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Sample records for oral tolerance induction

  1. Oral tolerance induction with altered forms of ovalbumin

    Directory of Open Access Journals (Sweden)

    Stransky B.

    1998-01-01

    Full Text Available As a T cell-dependent phenomenon, oral tolerance is not expected to depend necessarily on native configuration of antigens. We investigated the induction of oral tolerance with modified ovalbumin (Ova. Oral administration of heat-denatured (HD-Ova and cyanogen bromide-degraded ovalbumin was less effective than native Ova in inducing oral tolerance in B6D2F1 mice. HD-Ova was effective in suppressing delayed-type hypersensitivity (DTH reactions but did not suppress specific antibody formation. Injection of Ova directly into the stomach, but not into the ileum or cecum, suppressed subsequent immunization to DTH reactions. Gavage with protease inhibitors (aprotinin or ovomucoid before gavage with Ova was ineffective in blocking tolerance induction. Treatment with hydroxyurea to destroy cycling cells 24 h before gavage with Ova blocked oral tolerance induction and also the possibility to passively transfer tolerance to naive recipients with the serum of mice gavaged with Ova 1 h before. The implications of these findings about oral tolerance induction are discussed

  2. Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction

    Science.gov (United States)

    Wakabayashi, Ayako; Kumagai, Yoshihiro; Watari, Eiji; Shimizu, Masumi; Utsuyama, Masanori; Hirokawa, Katsuiku; Takahashi, Hidemi

    2006-01-01

    Oral administration of a certain dose of antigen can generally induce immunological tolerance against the same antigen. In this study, we showed the temporal appearance of ovalbumin (OVA) antigens in both portal and peripheral blood of mice after the oral administration of OVA. Furthermore, we detected 45 000 MW OVA in mouse serum 30 min after the oral administration of OVA. Based on this observation, we examined whether the injection of intact OVA into the portal or peripheral vein induces immunological tolerance against OVA. We found that the intravenous injection of intact OVA did not induce immunological tolerance but rather enhanced OVA-specific antibody production in some subclasses, suggesting that OVA antigens via the gastrointestinal tract but not intact OVA may contribute to establish immunological tolerance against OVA. Therefore, we examined the effects of digesting intact OVA in the gastrointestinal tract on the induction of oral tolerance. When mice were orally administered or injected into various gastrointestinal organs, such as the stomach, duodenum, ileum, or colon and boosted with intact OVA, OVA-specific antibody production and delayed-type hypersensitivity (DTH) response were significantly enhanced in mice injected into the ileum or colon, compared with orally administered mice. These results suggest that although macromolecular OVA antigens are detected after oral administration of OVA in tolerant-mouse serum, injection of intact OVA cannot contribute to tolerance induction. Therefore, some modification of macromolecular OVA in the gastrointestinal tract and ingestion may be essential for oral tolerance induction. PMID:16796692

  3. Erythromycin treatment hinders the induction of oral tolerance to fed ovalbumin

    Directory of Open Access Journals (Sweden)

    Sydney E. Lambert

    2012-07-01

    Full Text Available The mucosal immune system is constantly exposed to antigen, whether it be food antigen, commensal bacteria, or harmful antigen. It is essential that the mucosal immune system can distinguish between harmful and non-harmful antigens, and initiate an active immune response to clear the harmful antigens, while initiating a suppressive immune response (tolerance to non-harmful antigens. Oral tolerance is an immunologic hyporesponsiveness to an orally administered antigen and is important in preventing unnecessary gastrointestinal (GI tract inflammation, which can result in a number of autoimmune and hypersensitivity diseases. Probiotics (beneficial intestinal bacteria, T regulatory cells (Tregs, and dendritic cells (DCs are all essential for generating tolerance. Antibiotics are commonly prescribed to fight infections and often necessary for maintaining health, but they can disrupt the normal intestinal probiotic populations. There is increasing epidemiologic evidence that suggests that antibiotic usage correlates with the development of atopic or irritable bowel disorders, which often result due to a breakdown in immune tolerance. This study investigated the effect of the antibiotic erythromycin on oral tolerance induction to ovalbumin (OVA. The results demonstrated that antibiotic treatment prior to exposure to fed antigen prevents tolerance to that antigen, which may be associated with a reduction in intestinal Lactobacillus populations. Furthermore, antibiotic treatment resulted in a significant decrease in the tolerogenic CD11c+/CD11b+/CD8α- MLN DCs independent of tolerizing treatment. These results provide evidence that antibiotic treatment, potentially through its effects on tolerogenic DCs and intestinal microflora, may contribute to autoimmune and atopic disorders via a breakdown in tolerance and support prior epidemiologic studies correlating increased antibiotic usage with the development of these disorders.

  4. Expanding dendritic cells in vivo enhances the induction of oral tolerance.

    Science.gov (United States)

    Viney, J L; Mowat, A M; O'Malley, J M; Williamson, E; Fanger, N A

    1998-06-15

    The intestine is under perpetual challenge from both pathogens and essential nutrients, yet the mucosal immune system is able to discriminate effectively between harmful and innocuous Ags. It is likely that this selective immunoregulation is dependent on the nature of the APC at sites where gut Ags are processed and presented. Dendritic cells (DC) are considered the most potent of APC and are renowned for their immunostimulatory role in the initiation of immune responses. To investigate the role of DC in regulating the homeostatic balance between mucosal immunity and tolerance, we treated mice with Flt3 ligand (Flt3L), a growth factor that expands DC in vivo, and assessed subsequent systemic immune responsiveness using mouse models of oral tolerance. Surprisingly, mice treated with Flt3L to expand DC exhibited more profound systemic tolerance after they were fed soluble Ag. Most notably, tolerance could be induced in Flt3L-treated mice using very low doses of Ag that were ineffective in control animals. These findings contrast with the generally accepted view of DC as immunostimulatory APC and furthermore suggest a pivotal role for DC during the induction of tolerance following mucosal administration of Ag.

  5. Implementing specific oral tolerance induction to milk into routine clinical practice: experience from first 50 patients

    Directory of Open Access Journals (Sweden)

    Luyt D

    2014-01-01

    Full Text Available David Luyt, Kristian Bravin, Jessica Luyt Children's Allergy Service, University Hospitals of Leicester, Leicester, UK Background: Although the natural history of cow's milk allergy is to resolve during childhood or adolescence, a small but significant proportion of children will remain allergic. Specific oral tolerance induction to cow's milk (CM-SOTI provides a treatment option in these children with continuing allergy with high success rates. However current sentiment limits widespread availability as existing reports advise that it is too soon to translate CM-SOTI into routine clinical practice. Methods: In January 2007 we implemented a slow up-dosing CM-SOTI program. Eligible subjects were identified at routine visits to our children's allergy clinic. Persisting cow's milk allergy was confirmed from recent contact symptoms or a positive baked milk challenge. As allergic symptoms are common during CM-SOTI, families were provided with ready dietetic access for advice on dosing and symptom treatment. Subjects were continuously monitored at subsequent clinic visits or telephonically, where no longer followed, for a median of 49 months. Results: The first 50 subjects (35 males treated ranged in age from 5.1 to 15.8 years (median 10.3 years. Full tolerance (250 mL was achieved in 23 subjects, 9 without any symptoms, and a further 9 achieved partial tolerance with continued ingestion. Eighteen children failed to achieve any regular milk ingestion; 11 because of persistent or significant symptoms whilst 8 withdrew against medical advice. Allergic symptoms were predominantly mild to moderate in severity, although 2 cases needed treatment with inhaled salbutamol and a further 2 required intramuscular adrenaline. Clinical tolerance, both full and partial, persists beyond 5 years. Conclusion: We have demonstrated that a CM-SOTI program can be successfully and safely implemented as routine clinical practice with acceptable compliance during prolonged

  6. Specific Oral Tolerance Induction Using IFN-Gamma in 2 Cases of Food-Dependent Exercise-Induced Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Geunwoong Noh

    2013-01-01

    Full Text Available Anaphylaxis induced by exercise after the intake of certain foods is referred to as food-dependent exercise-induced anaphylaxis (FDEIA. Only the preventive medication such as oral sodium cromoglycate and oral combined cetirizine-montelukast was tried in FDEIA. Specific oral tolerance induction (SOTI using IFN-gamma was tried in 2 cases of FDEIA for wheat. Merely, exercise accompanied every treatment just after the intake of allergenic foods during treatment. Patients acquired tolerance for wheat in both cases successfully. After treatment, two patients take wheat in their food living freely. Conclusively, SOTI using IFN-gamma was effective as the causative treatment for allergenic foods in FDEIA.

  7. Induction of Oral Tolerance with Transgenic Plants Expressing Antigens for Prevention/Treatment of Autoimmune, Allergic and Inflammatory Diseases.

    Science.gov (United States)

    Ma, Shengwu; Liao, Yu-Cai; Jevnikar, Anthony M

    2015-01-01

    The prevalence and incidence of autoimmune and allergic diseases have increased dramatically over the last several decades, especially in the developed world. The treatment of autoimmune and allergic diseases is typically with the use of non-specific immunosuppressive agents that compromise the integrity of the host immune system and therefore, increase the risk of infections. Antigenspecific immunotherapy by reinstating immunological tolerance towards self antigens without compromising immune functions is a much desired goal for the treatment of autoimmune and allergic diseases. Mucosal administration of antigen is a long-recognized method of inducing antigen-specific immune tolerance known as oral tolerance, which is viewed as having promising potential in the treatment of autoimmune and allergic diseases. Plant-based expression and delivery of recombinant antigens provide a promising new platform to induce oral tolerance, having considerable advantages including reduced cost and increased safety. Indeed, in recent years the use of tolerogenic plants for oral tolerance induction has attracted increasing attention, and considerable progress has been made. This review summarizes recent advances in using plants to deliver tolerogens for induction of oral tolerance in the treatment of autoimmune, allergic and inflammatory diseases.

  8. Spontaneously relapsing-remitting experimental autoimmune uveitis in rats allows successful therapeutic oral tolerance induction in ongoing disease.

    Science.gov (United States)

    Huber, Andrea; Diedrichs-Möhring, Maria; Wildner, Gerhild

    2015-02-01

    Antigen-specific tolerance induction is a desired therapy for uveitis patients. Our relapsing-remitting rat model of experimental autoimmune uveitis (EAU) induced with IRBP peptide R14 enables us to test the effect of oral tolerance on the prevention of relapsing uveitis. We investigated several peptides overlapping the sequence of R14 for prevention and different doses of R14 for therapy to determine the tolerogenic epitope and the most effective therapeutic regimen for uveitis. Lewis rats were immunized with R14-CFA to induce EAU. Oral tolerance was induced prior to immunization (prevention) or after onset of EAU to prevent relapses (therapy). Therapeutic feeding was performed with high and/or low doses of oral antigen for clonal deletion of effector and induction of regulatory T cells. Uveitis was determined clinically and histologically; mesenteric lymph node (mLN) cells of tolerized rats were tested for surface markers, cytokines and Foxp3 expression. Preventive feeding of R14 and its major epitope R16, but none of the overlapping peptides significantly suppressed EAU and also prevented relapses, irrespective of their pathogenicity. Therapeutic feeding with R14 dramatically reduced relapses, while only the consecutive feeding of high and low-dose R14 had an ameliorating effect on the first course of disease. IL-10-producing T cells from mLN decreased after oral tolerization, and with R14-stimulation in vitro the TCRαβ+/Foxp3+ population increased in the low-dose fed group. No mLN population could be clearly assigned to successful oral tolerance induction during active autoimmune uveitis.

  9. Stabilization of serum antibody responses triggered by initial mucosal contact with the antigen independently of oral tolerance induction

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    B.A. Verdolin

    2001-02-01

    Full Text Available Initial contacts with a T-dependent antigen by mucosal routes may result in oral tolerance, defined as the inhibition of specific antibody formation after subsequent parenteral immunizations with the same antigen. We describe here an additional and permanent consequence of these initial contacts, namely, the blockade of secondary-type responsiveness to subsequent parenteral contacts with the antigen. When repeatedly boosted ip with small doses (3 µg of ovalbumin (OVA (or lysozyme, primed B6D2F1 mice showed progressively higher antibody responses. In contrast, mice primed after a single oral exposure to the antigen, although repeatedly boosted, maintained their secondary antibody titers on a level which was inversely proportional to the dose of antigen in the oral pretreatment. This phenomenon also occurred in situations in which oral tolerance was not induced. For example, senile 70-week-old B6D2F1 mice pretreated with a single gavage of 20 mg OVA did not become tolerant, i.e., they formed the same secondary levels of anti-OVA antibodies as non-pretreated mice. However, after 4 weekly challenges with 3 µg OVA ip, orally pretreated mice maintained the same anti-OVA serum levels, whereas the levels of control mice increased sequentially. This "stabilizing" effect of mucosal exposure was dose dependent, occurred with different proteins and was triggered by single or multiple oral or nasal exposures to the antigen.

  10. The GARP/Latent TGF-β1 complex on Treg cells modulates the induction of peripherally derived Treg cells during oral tolerance.

    Science.gov (United States)

    Edwards, Justin P; Hand, Timothy W; Morais da Fonseca, Denise; Glass, Deborah D; Belkaid, Yasmine; Shevach, Ethan M

    2016-06-01

    Treg cells can secrete latent TGF-β1 (LTGF-β1), but can also utilize an alternative pathway for transport and expression of LTGF-β1 on the cell surface in which LTGF-β1 is coupled to a distinct LTGF-β binding protein termed glycoprotein A repetitions predominant (GARP)/LRRC32. The function of the GARP/LTGF-β1 complex has remained elusive. Here, we examine in vivo the roles of GARP and TGF-β1 in the induction of oral tolerance. When Foxp3(-) OT-II T cells were transferred to wild-type recipient mice followed by OVA feeding, the conversion of Foxp3(-) to Foxp3(+) OT-II cells was dependent on recipient Treg cells. Neutralization of IL-2 in the recipient mice also abrogated this conversion. The GARP/LTGF-β1 complex on recipient Treg cells, but not dendritic cell-derived TGF-β1, was required for efficient induction of Foxp3(+) T cells and for the suppression of delayed hypersensitivity. Expression of the integrin αvβ8 by Treg cells (or T cells) in the recipients was dispensable for induction of Foxp3 expression. Transient depletion of the bacterial flora enhanced the development of oral tolerance by expanding Treg cells with enhanced expression of the GARP/LTGF-β1 complex.

  11. Effect of the gastrointestinal microflora on induction and maintenance of oral tolerance to ovalbumin in C3H/HeJ mice.

    OpenAIRE

    Moreau, M C; Corthier, G

    1988-01-01

    The effect of the digestive microflora on oral tolerance to ovalbumin was studied by using axenic (germfree) and conventional C3H/HeJ mice. In contrast to reported results of studies with sheep erythrocytes, oral administration of ovalbumin induced tolerance in axenic mice, but the maintenance of tolerance was found to be of shorter duration than was with conventional mice. These data indicate that the contribution of the microflora to oral tolerance depends on the antigen used.

  12. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

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    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  13. Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

    NARCIS (Netherlands)

    Maassen, C.B.M.; Laman, J.D.; Heijne den Bak-Glashouwer, M.J.; Tielen, F.J.; Holten-Neelen, J.C.P.A. van; Hoogteijling, L.; Antonissen, C.; Leer, R.J.; Pouwels, P.H.; Boersma, W.J.A.; Shaw, D.M.

    1999-01-01

    Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in

  14. Instruments for oral disease-intervention strategies : recombinant Lactobacillus casei expressing tetanus toxin fragment C for vaccination or myelin proteins for oral tolerance induction in multiple sclerosis

    NARCIS (Netherlands)

    Maassen, C.B.M.; Laman, J.D.; Heijne den Bak-Glashouwer, M.J.; Tielen, F.J.; Holten-Neelen, J.C.P.A. van; Hoogteijling, L.; Antonissen, C.; Leer, R.J.; Pouwels, P.H.; Boersma, W.J.A.; Shaw, D.M.

    1999-01-01

    Lactobacillus strains possess properties that make them attractive candidates as vehicles for oral administration of therapeutics. In this report we describe the construction and analysis of recombinant Lactobacillus casei applicable in oral vaccination against an infectious disease (tetanus) and in

  15. ORAL GLUCOSE TOLERANCE TEST REVISITED

    African Journals Online (AJOL)

    Determinant for the usefulness or otherwise of oral glucose tolerance test for the diagnosis ... personnel, poverty and poor economic management, 8'9 that are known to .... Symptoms of diabetes plus casual plasma glucose ... WHO 2-hr plasma glucose criteria of 1l.1mmol/L .... Diagnostic criteria and performance revisited.

  16. Modulation of ovomucoid-specific oral tolerance in mice fed plant extracts containing lectins

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    We investigated the effect of feeding extracts of four different legumes (red kidney bean (Phaseolus vulgaris), peanut (Arachis hypogaea), soyabean (Glycine max) and pea (Pisum sativum) on the specific immune response against a food protein. Mice were fed ovomucoid and the specific immune response...... was evaluated. Ovomucoid fed alone resulted in oral tolerance induction measured as both a reduced ovomucoid-pecific spleen cell proliferation and antibody response. Feeding kidney-bean extract prevented induction of oral tolerance to ovomucoid measured as spleen cell proliferation in vitro. Pure kidney......-bean lectin also prevented oral tolerance induction, suggesting that lectin in the kidney-bean extract caused inhibition of oral tolerance. Parenteral administration (intravenous and intraperitoneal) of pure kidney-bean lectin had no significant influence on oral tolerance induction. Soyabean extract also...

  17. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for

  18. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmun

  19. Strain-dependent induction of cytokine profiles in the gut by orally administered Lactobacillus strains

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, C. van; Balk, F.; Bak-Glashouwer, M.-J.H. den; Leer, R.J.; Laman, J.D.; Boersma, W.J.A.; Claassen, E.

    2000-01-01

    Different Lactobacillus strains are frequently used in consumer food products. In addition, recombinant lactobacilli which contain novel expression vectors can now be used in immunotherapeutic applications such as oral vaccination strategies and in T cell tolerance induction approaches for autoimmun

  20. Oral misoprostol for induction of labour.

    Science.gov (United States)

    Alfirevic, Zarko; Aflaifel, Nasreen; Weeks, Andrew

    2014-06-13

    Misoprostol is an orally active prostaglandin. In most countries misoprostol is not licensed for labour induction, but its use is common because it is cheap and heat stable. To assess the use of oral misoprostol for labour induction in women with a viable fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 January 2014). Randomised trials comparing oral misoprostol versus placebo or other methods, given to women with a viable fetus for labour induction. Two review authors independently assessed trial data, using centrally-designed data sheets. Overall there were 76 trials (14,412) women) which were of mixed quality.In nine trials comparing oral misoprostol with placebo (1109 women), women using oral misoprostol were more likely to give birth vaginally within 24 hours (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.05 to 0.49; one trial; 96 women), need less oxytocin (RR 0.42, 95% CI 0.37 to 0.49; seven trials; 933 women) and have a lower caesarean section rate (RR 0.72, 95% CI 0.54 to 0.95; eight trials; 1029 women).In 12 trials comparing oral misoprostol with vaginal dinoprostone (3859 women), women given oral misoprostol were less likely to need a caesarean section (RR 0.88, 95% CI 0.78 to 0.99; 11 trials; 3592 women). There was some evidence that they had slower inductions, but there were no other statistically significant differences.Nine trials (1282 women) compared oral misoprostol with intravenous oxytocin. The caesarean section rate was significantly lower in women who received oral misoprostol (RR 0.77, 95% CI 0.60 to 0.98; nine trials; 1282 women), but they had increased rates of meconium-stained liquor (RR 1.65, 95% CI 1.04 to 2.60; seven trials; 1172 women).Thirty-seven trials (6417 women) compared oral and vaginal misoprostol and found no statistically significant difference in the primary outcomes of serious neonatal morbidity/death or serious maternal morbidity or death. The results for vaginal birth not

  1. Specific oral tolerance induction for the treatment of food allergy%特异性口服免疫耐受治疗食物过敏的研究进展

    Institute of Scientific and Technical Information of China (English)

    周雪莲; 赵晓东

    2012-01-01

    儿童食物过敏(food allergy,FA)发病率有逐年增高趋势,双盲安慰剂激发试验是诊断食物过敏的金标准,回避不适宜食物是目前治疗食物过敏的标准方法.但严格的食物回避依从性较差,可能导致营养不良,长期饮食回避可增加意外摄入时产生严重过敏反应的风险.特异性口服免疫耐受(specific oral tolerance induction,SOTl)通过口服使患者过敏的蛋白抗原,刺激机体形成对该抗原无应答状态,是治疗食物过敏的新方向.由于缺乏双盲安慰剂激发试验,其有效性、安全性以及经济效益仍受到置疑,本文通过对特异性口服免疫耐受的方法、机制以及与传统治疗方法相比较,探讨其临床应用可能性.%The morbidity of food allergy in children has a tendency to increase these years. Double-blind placebo-controlled food challenge (DBPCFC) is the gold standard for the diagnosis of food allergy, and the standard treatment for food allergy is strict food avoidance. However, longtime strict food avoidance is difficult in everyday life, and may lead to malnutrition and even can increase the risk for developing severe ana-phylaxis after accidental ingestion. Specific oral tolerance induction (SOTI) is a new and possible way to treat food allergy, which is performed by limited ingestion of the allergen to make the body become unresponsive to it. However, the effectiveness, safety and economic benefit are still controversial, because of the deficiency of DBPCFC. Our paper will introduce the methods and mechanism of SOTI, compare it with traditional treatments for food allergy, and discuss the possibility of clinical use of SOTI.

  2. Titrated oral misoprostol solution- a new method of labour induction ...

    African Journals Online (AJOL)

    Titrated oral misoprostol solution- a new method of labour induction. ... a cheap, stable, orally active prostaglandin analogue, is effective for labour induction ... misoprostol doses commencing with 20 μg, increased after three doses to 40 μg.

  3. Participation of Leukotrienes in the Immune Modulation of Oral Tolerance

    Science.gov (United States)

    de Oliveira, Sandra R. P.; Nomizo, Auro; Frantz, Fabiani G.; Faccioli, Lúcia H.; de Matos, Ana Paula Keller; Carrilho, Emanuel; Afonso, Ana; de Freitas Anibal, Fernanda

    2017-01-01

    Oral tolerance (OT) is characterized as a peripheral immune tolerance form, in which, mature lymphocytes in lymphoid tissues associated with mucosa, become non-functional or hypo responsive due to prior oral administration of antigen. OT is an important immunological phenomenon due to its therapeutic potential in inflammatory processes and others diseases. Here we evaluated leukotriene role in the induction of OT, as well as, the production of cytokines IL-5 and IFN-γ in leukotriene deficient animals (knock-out). Our results suggested that even in the presence of OT and leukotrienes absence, cytokine IFN-γ remains being secreted, which gives us an indication of immune system specificity and also that IFN-γ participates in various immune processes. PMID:28270799

  4. Oral vaccination of fish- antigen preparations, uptake and immune induction

    Directory of Open Access Journals (Sweden)

    Stephen eMutoloki

    2015-10-01

    Full Text Available The oral route offers the most attractive approach of immunization of fish for a number of reasons: the ease of administration of antigens, it is less stressful than parenteral delivery and in principle, it is applicable to small and large sized fish; it also provides a procedure for oral boosting during grow-out periods in cages or ponds. There are however not many commercial vaccines available at the moment due to lack of efficacy and challenges associated with production of large quantities of antigens. These are required to stimulate an effective immune response locally and systemically, and need to be protected against degradation before they reach the sites where immune induction occurs. The hostile stomach environment is believed to be particularly important with regard to degradation of antigens in certain species. There is also a poor understanding about the requirements for proper immune induction following oral administration on one side, and the potential for induction of tolerance on the other. To what extent primary immunization via the oral route will elicit both local and systemic responses is not understood in detail. Furthermore, to what extent parenteral delivery will protect mucosal/gut surfaces and vice-versa is also not fully understood. We review the work that has been done on the subject and discuss it in light of recent advances that include mass production of antigens including the use of plant systems. Different encapsulation techniques that have been developed in the quest to protect antigens against digestive degradation, as well as to target them for appropriate immune induction are also highlighted.

  5. Hitting the mucosal road in tolerance induction.

    Science.gov (United States)

    Wiedermann, Ursula

    2009-01-01

    Within the last decades a dramatic increase in allergic diseases has been recognized in the Westernized societies, leading to the fact that meanwhile 25-30% of the population is afflicted by allergic disorders. Besides a hereditary disposition, other factors, including a reduced microbial contact early in life or changes in nutrition, might also have influenced this epidemiological development. So far the only causative treatment against type-I allergies is specific immunotherapy. In young and monosensitized patients this treatment is highly efficacious, while there are clear limitations in older or multisensitized patients. Allergy research therefore aims at establishing new and more efficacious treatment strategies in prophylactic as well as therapeutic settings. Our research programs focus on the development of novel allergy vaccines based on the induction of mucosal tolerance. In different mouse models of respiratory allergy mucosal treatment with genetically engineered allergen constructs proved to prevent the development of allergic mono- and multisensitivities. The additional use of mucosal adjuvants seems particularly important to improve therapeutic treatment approaches. Recent studies on the inverse relation of certain parasite infections and the development of allergy prompted us to search for selected parasitic molecules with immunosuppressive properties as potential adjuvant systems for novel allergy vaccines. An overview of our recent studies will be given.

  6. Food allergen selective thermal processing regimens may change oral tolerance in infancy.

    Science.gov (United States)

    Kosti, R I; Triga, M; Tsabouri, S; Priftis, K N

    2013-01-01

    Food allergy can be considered a failure in the induction of oral tolerance. Recently, great interest has been focused on understanding the mechanisms and the contributing factors of oral tolerance development, hoping for new definitive interventions in the prevention and treatment of food allergy. Given that food processing may modify the properties and the nature of dietary proteins, several food processing methods could affect the allergenicity of these proteins and consequently may favour oral tolerance induction to food allergic children. Indeed, effective thermal food processing regimens of altering food proteins to reduce allergenicity have been recently reported in the literature. This article is mainly focused on the effect of selective thermal processing regimens on the main infant allergenic foods, with a potential clinical relevance on their allergenicity and therefore on oral tolerance induction. In the light of recent findings, the acquisition of tolerance in younger age and consequently the ability of young children to "outgrow" food allergy could be achieved through the application of selective thermal processing regimens on certain allergenic foods. Therefore, the ability of processed foods to circumvent clinical disease and at the same time to have an impact on the immune system and facilitate tolerance induction could be invaluable as a component of a successful therapeutic strategy. The opening in the new avenues of research in the use of processed foods in clinical practice for the amelioration of the impact on the quality of life of patients and possibly in food allergy prevention is warranted.

  7. Induction of immunologic tolerance to collagen induced arthritis mice by oral administration of chicken type Ⅱ collagen%口服鸡源性Ⅱ型胶原蛋白诱导实验性CIA小鼠免疫耐受

    Institute of Scientific and Technical Information of China (English)

    李卫东; 冉国侠; 沈建英; 滕惠玲; 林志彬

    2000-01-01

    Objective: To assess the immunological effects by orally administering chicken type Ⅱ collagen(CCⅡ) on collagen-induced arthritis(CIA)mice. To assess the effect on producing IL-1 of peritoneal macrophage in adjuvant arthritis rats by orally administering CCⅡ. Methods: Arthritis were induced in Kunming mice by immunization with chicken type Ⅱ collagen with Freund's complete adjuvant, followed by an interperitoneal injection of CCⅡ 3 weeks later.Chicken type Ⅱ collagen was orally administered from 5 days prior to the induction of arthritis to 14 days after inducing arthritis model. The animals were examined visually twice weekly for polyarthritic signs of swollen and erythemic limbs. Quantitation of antibody level of CIA mice was measured by ELISA method. Subpopulations of T lymphocytes in mice were evaluated by flow cytometry method. IL-1 assay was evaluated by ELISA method. Results: Joint swelling was significantly reduced at a dose of 5 μg.kg-1 and 50 μg.kg-1 of CCⅡ, but not at 250 μg.kg-1. The level of anti-collagen antibodies was also reduced at a dose of 5 μg.kg-1 and 50μg.kg-1 (OD value from CIA model control 0.242±0.073 to CCⅡ 5 μg.kg-1 0.123±0.029 and CCⅡ 50 μg.kg-1 0.110±0.075 respectively). Subpopulations of T-lymphocytes were changed by orally administering of CCⅡ, and the ratio of L3T4+/Lyt-2+ was lowered (the ratio from 1.71 of CIA model control to 1.21, 1.51 of administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively.) after administering CCⅡ. IL-1 level can be reduced (the value from adjuvant arthritis model control 62.8±0.9 to 43.4±1.3, 49.7±0 ng.L-1 administered CⅡ 5 μg.kg-1, 50μg.kg-1 respectively). Conclusion: Arthritis sign in CIA animal model can be suppressed by oral CCⅡ. The effects may be involved by influencing the mechanisms both humoral and cellular immunity. The effects occurred at lower doses of CCⅡ. These results demonstrated the biologic relevance of by-stander suppression associated with oral

  8. Oral tolerance to cancer can be abrogated by T regulatory cell inhibition.

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    Maria C Whelan

    Full Text Available Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue--JBS fibrosarcoma (to induce oral tolerance to a cancer, or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6% and faster tumour growth rates than controls (p<0.05. Complete regression of tumours were only seen after Treg inactivation and occurred in all groups--this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour

  9. Immune tolerance elicited via unique ocular and oral routes.

    Science.gov (United States)

    Ashour, H M

    2015-01-01

    Immune tolerance can be induced by numerous methods. This review article aims to draw lines of similarity and contrast between two unique models of immune tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel-induced oral tolerance. ACAID is an immune tolerance model that leads to the generation of CD4(+) T regulatory cells and CD8(+) T regulatory cells in the periphery after the injection of an antigen into the anterior chamber of the eye. Nickel-induced oral tolerance is another immune tolerance model that is induced by the contact allergen Nickel and leads to the generation of Nickel-specific CD4(+) CD25(+) T regulatory cells after oral exposure. The goal of comparing different models of immune tolerance is to identify which mechanisms are universal and which mechanisms are model-specific. The knowledge of such mechanisms would allow scientists and clinicians to better intervene in different immune deregulation scenarios.

  10. Donor chimera model for tolerance induction in transplantation

    NARCIS (Netherlands)

    Rezaee, F.; Peppelenbosch, M.; Dashty, M.

    Tolerance induction is the basis of a successful transplantation with the goal being the re-establishment of homeostasis after transplantation. Non-autograft transplantation disrupts this maintenance drastically which would be avoided by administration of a novel procedure. At present, the blood

  11. Facilitated Peptide Transport via the Mucosal Epithelium: Impact on Tolerance Induction

    Science.gov (United States)

    Kenngott, Elisabeth E.; Pfeil, Jennifer; Hoffmann, Ute; Lauer, Uta; Kühl, Anja A.; Rigby, Anne; Pernthaner, Anton; Hamann, Alf

    2017-01-01

    A hallmark of autoimmunity is the breakdown of tolerance and generation of effector responses against self-antigens. Re-establishment of tolerance in autoimmune disorders was always the most desired treatment option; however, despite many efforts, clinical trials have been largely unsuccessful. This also applies to the generation of oral tolerance, which seems to be a default response type of the mucosa-associated lymphoid tissues to harmless antigens. In this study, we report improved efficacy of oral tolerance induction by coupling antigen with the newly identified mucosal carrier peptide 13C. Antigen coupled to 13C is efficiently taken up in the gastrointestinal tract and could be visualized in cells of the lamina propria. Oral, rectal, or nasal treatment effectively induced the proliferation of antigen-specific T cells with some increase in the frequency of regulatory T cells. In a model of delayed-type hypersensitivity, especially intrarectal tolerization treatment resulted in reduced footpad swelling, demonstrating a moderate tolerogenic effect of mucosal treatment with 13C coupled antigen. Coupling of antigens to a transmucosal carrier, therefore, is a promising tool to improve the efficacy of vaccination via mucosal surfaces.

  12. Cutting Edge: A Critical Role of B and T Lymphocyte Attenuator in Peripheral T Cell Tolerance Induction1

    Science.gov (United States)

    Liu, Xikui; Alexiou, Maria; Martin-Orozco, Natalia; Chung, Yeonseok; Nurieva, Roza I.; Ma, Li; Tian, Qiang; Kollias, George; Lu, Sijie; Graf, Daniel; Dong, Chen

    2009-01-01

    T cell activation and tolerance are delicately regulated by costimulatory molecules. Although B and T lymphocyte attenuator (BTLA) has been shown as a negative regulator for T cell activation, its role in peripheral T cell tolerance induction in vivo has not been addressed. In this study, we generated a novel strain of BTLA-deficient mice and used three different models to characterize the function of BTLA in controlling T cell tolerance. In an oral tolerance model, BTLA-deficient mice were found resistant to the induction of T cell tolerance to an oral Ag. Moreover, compared with wild-type OT-II cells, BTLA−/− OT-II cells were less susceptible to tolerance induction by a high-dose OVA peptide administered i.v. Finally, BTLA−/− OT-I cells caused auto-immune diabetes in RIP-mOVA recipient mice. Our results thus demonstrate an important role for BTLA in the induction of peripheral tolerance of both CD4+and CD8+ T cells in vivo. PMID:19342624

  13. Oral Tolerance: A New Tool for the Treatment of Gastrointestinal Inflammatory Disorders and Liver-Directed Gene Therapy

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    Yaron Ilan

    1999-01-01

    Full Text Available Oral tolerance is a method of downregulating an immune response by feeding antigens. The use of oral tolerance toward adenoviruses and colitis-extracted proteins for long term gene therapy and alleviation of experimental colitis, and the mechanisms of tolerance induction are presented. Adenoviruses are efficient vectors in liver-directed gene therapy; however, the antiviral immune response precludes the ability to achieve long term gene expression and prohibits the ability to reinject the recombinant virus. Oral tolerance induction via feeding of viral-extracted proteins prevented the antiadenoviral humoral and cellular immune responses, thus enabling long term gene therapy using these viruses. Moreover, pre-existing immune response to the virus was overcome by tolerance induction, enabling prolonged gene expression in a presensitized host. Inflammatory bowel diseases are immune-mediated disorders where an imbalance between proinflammatory (T helper cell type 1 and anti-inflammatory (T helper cell type 2 cytokines are thought to play a role in the pathogenesis. In the experimental colitis model, the feeding of colitis-extracted proteins downregulated the anticolon immune response. Tolerance induction toward colitis-extracted proteins ameliorated colonic inflammation as shown by decreased diarrhea and reduction of colonic ulcerations, intestinal and peritoneal adhesions, wall thickness and edema. Histological parameters for colitis were markedly improved in tolerized animals. In both models, tolerized animals developed an increase in transforming growth factor-beta, interleukin-4 and interleukin-10, and a decrease in the mRNA of interferon-gamma lymphocytes and serum levels. Adoptive transfer of tolerized lymphocytes enabled the transfer of tolerance toward adenoviruses and colon-extracted proteins. Thus, oral tolerance induces suppressor lymphocytes that mediate immune response downregulation by induction of a shift from a proinflammatory T

  14. Indirect Effects of Oral Tolerance Inhibit Pulmonary Granulomas to Schistosoma mansoni Eggs

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    Geraldo Magela Azevedo

    2012-01-01

    Full Text Available Parenteral injection of tolerated proteins into orally tolerant mice inhibits the initiation of immunological responses to unrelated proteins and blocks severe chronic inflammatory reactions of immunological origin, such as autoimmune reactions. This inhibitory effect which we have called “indirect effects of oral tolerance” is also known as “bystander suppression.” Herein, we show that i.p. injection of OVA + Al(OH3 minutes before i.v. injection of Schistosoma mansoni eggs into OVA tolerant mice blocked the increase of pulmonary granulomas. In addition, the expression of ICAM-1 in lung parenchyma in areas outside the granulomas of OVA-orally tolerant mice was significantly reduced. However, at day 18 after granuloma induction there was no difference in immunofluorescency intensity to CD3, CD4, F4/80, andα-SMA per granuloma area of tolerant and control groups. Reduction of granulomas by reexposure to orally tolerated proteins was not correlated with a shift in Th-1/Th-2 cytokines in serum or lung tissue extract.

  15. Induction of systemic stress tolerance by brassinosteroid in Cucumis sativus.

    Science.gov (United States)

    Xia, Xiao-Jian; Zhou, Yan-Hong; Ding, Ju; Shi, Kai; Asami, Tadao; Chen, Zhixiang; Yu, Jing-Quan

    2011-08-01

    • Brassinosteroids (BRs) are a new class of plant hormones that are essential for plant growth and development. Here, the involvement of BRs in plant systemic tolerance to biotic and abiotic stresses was studied. • The effects of 24-epibrassinolide (EBR) on plant stress tolerance were studied through the assessment of symptoms of photooxidative stress by chlorophyll fluorescence imaging pulse amplitude modulation, the analysis of gene expression using quantitative real-time PCR and the measurement of hydrogen peroxide (H₂O₂) production using a spectrophotometric assay or confocal laser scanning microscopy. • Treatment of primary leaves with EBR induced systemic tolerance to photooxidative stress in untreated upper and lower leaves. This was accompanied by the systemic accumulation of H₂O₂ and the systemic induction of genes associated with stress responses. Foliar treatment of EBR also enhanced root resistance to Fusarium wilt pathogen. Pharmacological study showed that EBR-induced systemic tolerance was dependent on local and systemic H₂O₂ accumulation. The expression of BR biosynthetic genes was repressed in EBR-treated leaves, but elevated significantly in untreated systemic leaves. Further analysis indicated that EBR-induced systemic induction of BR biosynthetic genes was mediated by systemically elevated H₂O₂. • These results strongly argue that local EBR treatment can activate the continuous production of H₂O₂, and the autopropagative nature of the reactive oxygen species signal, in turn, mediates EBR-induced systemic tolerance.

  16. Immune tolerance induction for laronidase treatment in mucopolysaccharidosis I.

    Science.gov (United States)

    Giugliani, Roberto; Vieira, Taiane Alves; Carvalho, Clarissa Gutierrez; Muñoz-Rojas, Maria-Veronica; Semyachkina, Alla N; Voinova, Victoria Y; Richards, Susan; Cox, Gerald F; Xue, Yong

    2017-03-01

    Enzyme replacement therapy (ERT) can produce anti-drug antibody (ADA) responses that reduce efficacy or lead to hypersensitivity reactions. Six patients with severe mucopolysaccharidosis type I (MPS I/Hurler syndrome) who did not receive hematopoietic stem cell transplantation underwent an immunosuppression regimen prior to initiating ERT with laronidase. The primary endpoint for immune tolerance induction was the number of patients with an ADA titer ≤ 3200 after 24 weeks of laronidase at the labeled dose. Cyclosporine levels were measured weekly and doses adjusted to maintain trough levels above 400 mg/mL. A 6-week (Cohort 1) or 12-week (Cohort 2) immune tolerance induction period with cyclosporine (initial dose: 15 or 20 mg/kg/day), azathioprine (initial dose: 2.5 or 5 mg/kg/day) and low-dose laronidase infusions (0.058-0.29 mg/kg/week) was followed by an immune-challenge period with laronidase infusions at the labeled dose (0.58 mg/kg/week) for 24 weeks. Anti-laronidase IgG titers were determined following treatment. There were 147 treatment-emergent adverse events reported, most of which were mild and not related to the study treatment. While there was no evidence of immune tolerance in 3 of 3 patients in Cohort 1, there were some indications of immune tolerance induction in 2 of 3 patients in Cohort 2. Patients with lower ADA titers showed greater reductions in urinary glycosaminoglycan excretion. Routine monitoring of plasma cyclosporine parent-compound levels by high pressure liquid chromatography proved difficult for clinical practice. The evolving clinical management of MPS I and a better understanding of the clinical impact of laronidase-related immunogenicity require reassessment of immune modulation strategies in patients with MPS I receiving laronidase treatment.

  17. Fault tolerant vector control of induction motor drive

    Science.gov (United States)

    Odnokopylov, G.; Bragin, A.

    2014-10-01

    For electric composed of technical objects hazardous industries, such as nuclear, military, chemical, etc. an urgent task is to increase their resiliency and survivability. The construction principle of vector control system fault-tolerant asynchronous electric. Displaying recovery efficiency three-phase induction motor drive in emergency mode using two-phase vector control system. The process of formation of a simulation model of the asynchronous electric unbalance in emergency mode. When modeling used coordinate transformation, providing emergency operation electric unbalance work. The results of modeling transient phase loss motor stator. During a power failure phase induction motor cannot save circular rotating field in the air gap of the motor and ensure the restoration of its efficiency at rated torque and speed.

  18. Fault Tolerant Robust Control Applied for Induction Motor (LMI approach

    Directory of Open Access Journals (Sweden)

    Hamouda KHECHINI

    2007-09-01

    Full Text Available This paper foregrounds fault tolerant robust control of uncertain dynamic linear systems in the state space representation. In fact, the industrial systems are more and more complex and the diagnosis process becomes indispensable to guarantee their surety of functioning and availability, that’s why a fault tolerant control law is imperative to achieve the diagnosis. In this paper, we address the problem of state feedback H2 /H∞ mixed with regional pole placement for linear continuous uncertain system. Sufficient conditions for feasibility are derived for a general class of convex regions of the complex plan. The conditions are presented as a collection of linear matrix inequalities (LMI 's. The efficiency and performance of this approach are then tested taking into consideration the robust control of a three- phase induction motor drive with the fluctuation of its parameters during the functioning.

  19. Evaluation of Oral Glucose Tolerance Test in Children With Epilepsy.

    Science.gov (United States)

    Varlamis, Sotirios; Vavatsi, Norma; Pavlou, Evangelos; Kotsis, Vasileios; Spilioti, Martha; Kavga, Maria; Varlamis, George; Sotiriadou, Foteini; Agakidou, Eleni; Voutoufianakis, Spyridon; Evangeliou, Athanasios E

    2013-11-01

    Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P epilepsies from the drug-controlled ones and the first-induced seizures relating to their metabolic profile, regardless of the type of seizures.

  20. Immune tolerance induction in haemophilia: evidence and the way forward.

    Science.gov (United States)

    Di Michele, D M

    2011-07-01

    Given the inhibitor-associated morbidity resulting from limited effective treatment options, antibody eradication is the ultimate goal of inhibitor management. The only clinically proven strategy for achieving antigen-specific tolerance to factor VIII is immune tolerance induction (ITI). First reported over 30 years ago, much of our current knowledge about ITI in haemophilia A and B was derived from small cohort studies and retrospective national and international ITI registries. More recently, prospective randomised ITI trials have been designed and initiated to answer outstanding questions related to the optimisation of current therapeutic strategy in haemophilia A. However, due to the low incidence of inhibitor development in haemophilia B compared to haemophilia A, there are few comparable data from which to develop a useful evidence-based approach to the prevention and eradication of FIX inhibitors. The lack of an effective strategy is particularly problematic given the even greater morbidity associated with the almost unique occurrence of allergic and anaphylactic reactions that often herald FIX antibody development, and further complicates attempts to eradicate FIX inhibitors. Ultimately, successful inhibitor prevention and eradication strategies for both diseases will emerge from the clinical translation of our evolving knowledge of immune stimulation and tolerance. This paper will discuss our current understanding of immune tolerance outcome and outcome predictors for haemophilia A and B; it will also review the current consensus recommendations for ITI, as well as the emerging scientific body of immunological knowledge that may significantly impact the therapeutic and preventative strategies of the future.

  1. Oral misoprostol versus dinoprostone vaginal tablets for labor induction

    Directory of Open Access Journals (Sweden)

    Khaled Ibrahim Abu El aish

    2013-06-01

    Full Text Available Background: Induction of labour is common in obstetric practice. We conducted this study to find the appropriate and safe drug for labour induction and to compare the safety and efficacy of oral misoprostol and vaginal dinoprostone for labour induction. Methods: In a provisional, prospective and cross-sectional study, one hundred and fifty five singleton cephalic presentation full term pregnancies with medical or obstetric indication for labour induction were allocated in two groups. First group received oral 50 micrograms for nulliparas and low parity group (1-4, and 25micrograms for grand multiparas (≥ 5 misoprostol orally every 6 hours to a maximum of four doses daily. In the second group vaginal tablets of dinoprostone 3mg then 1.5mg for nulliparas and 1.5mg for low parity and grand multiparas groups were inserted in the posterior fornix, every 8 hours. Primary outcome measures were: induction success, induction-delivery interval and number of used doses. Secondary outcome measures included: maternal side effects, caesarean section rate, mode of delivery and neonatal outcome. Data was collected from patient case notes and analyzed using software SPSS (version 13.0 and p-value < 0.05 was used as statistical significance of differences. Results: In our study there were no significant differences in baseline parameters in the two groups nor in the indications for labor induction except misoprostol was used in premature rupture of membrane. Induction of labor succeeded in 123 (79.35% women without other interventions from other methods (80.26%misoprostol group versus 78.5% dinoprostone p=0.492. It was observed that there were no significant differences between the two groups in final outcomes nor in obstetrical complications. There was no significance in differences between misoprostol and dinoprostone groups in induction-delivery interval (15.2 ± 14.5 hours versus 16.4 ± 11.3 hours p=0.6 resp.. Conclusions: This study demonstrated that oral

  2. Immune tolerance induction in patients with hemophilia A.

    Science.gov (United States)

    Astermark, Jan

    2011-01-01

    Replacement therapy with factor VIII (FVIII) concentrates has become the mainstay of treatment for hemophilia, but about 30% of patients with a severe disease develop neutralizing antibodies against FVIII, which can lead to treatment resistance and an increased risk of bleeding. Immune tolerance induction (ITI) overcomes the immune response to FVIII concentrates in the majority of patients. Several factors may influence the efficacy of ITI, including disease-related factors (e.g. peak inhibitor titer and pre-ITI titer), and genetic factors (e.g. type of mutation). Treatment-related factors, such as the type of FVIII concentrate used in ITI will also potentially influence the outcome. Specifically, higher success rates with von Willebrand factor (VWF)-containing factor VIII concentrates than with high-purity FVIII concentrates have been reported, but further studies are needed. Potential mechanisms involved include steric hindrance, inhibition of FVIII degradation, or immunomodulatory effects. However, the exact mechanism by which immune tolerance is induced remains unclear. High-dose FVIII ITI appears to induce immune tolerance more rapidly than low-dose protocols and with a reduced risk of bleeding episodes. The addition of immunosuppressive therapy, such as rituximab, to ITI may improve outcomes, although the optimal approach to combined ITI/immunosuppression has not been established. Ongoing studies are likely to provide further insight into the role of genetic features and the type of FVIII concentrate on the success rate of ITI.

  3. Transplant Tolerance Induction in Newborn Infants: Mechanisms, Advantages, and Potential Strategies

    Science.gov (United States)

    Pan, Hua; Gazarian, Aram; Dubernard, Jean-Michel; Belot, Alexandre; Michallet, Marie-Cécile; Michallet, Mauricette

    2016-01-01

    Although several tolerance induction protocols have been successfully implemented in adult renal transplantation, no tolerance induction approach has, as yet, been defined for solid organ transplantations in young infants. Pediatric transplant recipients have a pressing demand for the elaboration of tolerance induction regimens. Indeed, since they display a longer survival time, they are exposed to a higher level of risks linked to long-term immunosuppression (IS) and to chronic rejection. Interestingly, central tolerance induction may be of great interest in newborns, because of their immunological immaturity and the important role of the thymus at this early stage in life. The present review aims to clarify mechanisms and strategies of tolerance induction in these immunologically premature recipients. We first introduce the discovery and mechanisms of neonatal tolerance in murine experimental models and subsequently analyze tolerance induction in human newborn infants. Hematopoietic mixed chimerism in neonates is also discussed based on in utero hematopoietic stem cell (HSC) transplant studies. Then, we review the recent advances in tolerance induction approaches in adults, including the infusion of HSCs associated with less toxic conditioning regimens, regulatory T cells/facilitating cells/mesenchymal stem cells transplantation, costimulatory blockade, and thymus manipulation. Finally, IS withdrawal in pediatric solid organ transplant is discussed. In conclusion, the establishment of transplant tolerance induction in infants is promising and deserves further investigations. Future studies could focus on the selection of patients, on less toxic conditioning regimens, and on biomarkers for IS minimization or withdrawal. PMID:27092138

  4. The Oral Tolerance as a Complex Network Phenomenon.

    Science.gov (United States)

    Miranda, Pedro Jeferson; Delgobo, Murilo; Marino, Giovani Favero; Paludo, Kátia Sabrina; da Silva Baptista, Murilo; de Souza Pinto, Sandro Ely

    2015-01-01

    The phenomenon of oral tolerance refers to a local and systemic state of tolerance induced in the gut after its exposure to innocuous antigens. Recent findings have shown the interrelationship between cellular and molecular components of oral tolerance, but its representation through a network of interactions has not been investigated. Our work aims at identifying the causal relationship of each element in an oral tolerance network, and also to propose a phenomenological model that's capable of predicting the stochastic behavior of this network when under manipulation. We compared the changes of a "healthy" network caused by "knock-outs" (KOs) in two approaches: an analytical approach by the Perron Frobenius theory; and a computational approach, which we describe within this work in order to find numerical results for the model. Both approaches have shown the most relevant immunological components for this phenomena, that happens to corroborate the empirical results from animal models. Besides explain in a intelligible fashion how the components interacts in a complex manner, we also managed to describe and quantify the importance of KOs that hasn't been empirically tested.

  5. Induction of allergen-specific tolerance via mucosal routes.

    Science.gov (United States)

    Mascarell, Laurent; Zimmer, Aline; Van Overtvelt, Laurence; Tourdot, Sophie; Moingeon, Philippe

    2011-01-01

    Allergen-specific immunotherapy is the only curative treatment of allergies against insect venom, house dust mites, tree/grass pollens, or cat dander. Subcutaneous immunotherapy is successful to reorient the immune system and re-establish long-term tolerance. However, major drawbacks for using this route include: repeated injections, as well as the risk of anaphylaxis. In this context, alternative mucosal routes of administration are being considered together with the combined use of adjuvants/vector systems and recombinant allergens or peptide fragments. Herein, we review the current status in the use of mucosal routes (i.e., sublingual, oral, intranasal) for allergen-specific immunotherapy, as well as the latest understanding with respect to underlying mechanisms of action.

  6. Cross-suppression of specific immune responses after oral tolerance

    Directory of Open Access Journals (Sweden)

    Nelson M. Vaz

    1981-03-01

    Full Text Available Adult normal inbred mice rendered tolerant to OVA by previous oral exposure do not respond to intraperitonela immunization with DNP-OVA in adjuvant. These tolerant mice also form less DNP-specific antibodies to DNP-KLH when immunized with mixtures of DNP-KLH and DNP-OVA, or less HGG-specific antibodies when immunized with cross-linked conjugates of OVA and HGG. These same procedures increased DNP-specific or HGG-specific responses in non-tolerant control mice. The cross-supperssion was ineffective, however, to inhibit already ongoing antibody responses.Camundongos adultos normais tornados imunologicamente tolerantes a ovoalbumina (OVA por exposição oral não formam anticorpos antidinitrofenil (anti-DNP quando imunizados com DNP-OVA, mas respondem normalmente à DNP-hemocianina (DNO-KLH. Entretanto, a adição de DNP-OVA à injeção de DNP-KLH reduz a formação de anticorpos anti-DNP em animais tolerantes a OVA, mas não em animais normais. Similarmente animais tolerantes à OVA formam menos anticorpos antiglobulina humana (HGG quando imunizados com agregados (por glutaraldeído de OVA e HGG. A tolerância oral e, portanto, capaz de inibir a indução de respostas imunes por um esquema de supressão-cruzada. Esse esquema, no entanto, não foi capaz de inibir respostas imunes já iniciadas.

  7. Effects of appendectomy and oral tolerance on dextran sulfate sodium colitis

    Institute of Scientific and Technical Information of China (English)

    Min Yue; Zhe Shen; Chao-Hui Yu; Hua Ye; Yue-Fang Ye; You-Ming Li

    2011-01-01

    AIM: To evaluate the concomitant effects of appendectomy and oral tolerance on colitis. METHODS: Delayed-type hypersensitivity (DTH) was investigated at a 7-d interval after ovalbumin (OVA) administration and immunization under normal and colitis conditions in appendectomized or sham-operated mice. Pathological scores for the colon were graded after ingestion of colon-extracted protein (CEP) and induction of dextran sulfate sodium (DSS) colitis in appendectomized or sham-operated mice. Thereafter, Th1 and Th2 in Peyer's patches and spleen lymphocytes were detected in CEP-treated and bovine serum albumin (BSA)-treated control mice. RESULTS: In appendectomized mice, DTH was not inhibited at day 7 after OVA administration and at the initial phase of DSS colitis, whereas it was inhibited at day 14 and day 21. However, in sham-operated mice, it was inhibited during the whole procedure and the onset of DSS colitis. The protective role of CEP against DSS colitis was present in sham-operated mice, with predominant improvement of colonic pathological changes, while vanished in the appendectomized mice. A shift from Th1 to Th2 in Peyer's patches resulted from a decrease of Th1 cells with the ingestion of CEP. Compared with BSA in the sham-operated group, no predominant changes were observed in the appendectomized mice. CONCLUSION: Appendectomy interferes with the protective role of CEP in DSS colitis via a shift from Th2 to Th1 during oral tolerance induction.

  8. Tolerance induction and transplantation of the mouse heart

    Energy Technology Data Exchange (ETDEWEB)

    Jirsch, D.W.; Kraft, N.; Diener, E.

    1973-01-01

    Long-surviving cardiac allografts can be produced by repopulating irradiated mice with steam cell rich fractions of syngeneic mouse spleen but not bone marrow. Short-term discontinuous HAMTS treatment of irradiated allografted mice can also render mice specifically tolerant. Spleen cells from animals tolerant to cardiac allografts remain reactive to alloantigens in vitro. Lymph node cells from tolerant mice are immunosuppressive and transfer tolerance when injected with whole bone marrow into secondary irradiated, allografted recipients.

  9. Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity.

    Science.gov (United States)

    Hugues, Stéphanie; Fetler, Luc; Bonifaz, Laura; Helft, Julie; Amblard, François; Amigorena, Sebastian

    2004-12-01

    Induction of immunity and peripheral tolerance requires contacts between antigen-bearing dendritic cells (DCs) and cognate T cells. Using real-time two-photon microscopy, we have analyzed the dynamics of CD8(+) T cells in lymph nodes during the induction of antigen-specific immunity or tolerance. At 15-20 h after the induction of immunity, T cells stopped moving and established prolonged interactions with DCs. In tolerogenic conditions, despite effective initial T cell activation and proliferation, naive T cells remained motile and established serial brief contacts with multiple DCs. Thus, stable DC-T cell interactions occur during the induction of priming, whereas brief contacts may contribute to the induction of T cell tolerance.

  10. Vagotomy affects the development of oral tolerance and increases susceptibility to develop colitis independently of the alpha-7 nicotinic receptor.

    Science.gov (United States)

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy

    2016-06-14

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR(-/-) mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR(-/-) mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR.

  11. Mechanisms of Tolerance Induction by Hematopoietic Chimerism: The Immune Perspective.

    Science.gov (United States)

    Yolcu, Esma S; Shirwan, Haval; Askenasy, Nadir

    2017-03-01

    Hematopoietic chimerism is one of the effective approaches to induce tolerance to donor-derived tissue and organ grafts without administration of life-long immunosuppressive therapy. Although experimental efforts to develop such regimens have been ongoing for decades, substantial cumulative toxicity of combined hematopoietic and tissue transplants precludes wide clinical implementation. Tolerance is an active immunological process that includes both peripheral and central mechanisms of mutual education of coresident donor and host immune systems. The major stages include sequential suppression of early alloreactivity, establishment of hematopoietic chimerism and suppressor cells that sustain the state of tolerance, with significant mechanistic and temporal overlap along the tolerization process. Efforts to devise less toxic transplant strategies by reduction of preparatory conditioning focus on modulation rather than deletion of residual host immunity and early reinstitution of regulatory subsets at the central and peripheral levels. Stem Cells Translational Medicine 2017;6:700-712.

  12. Importance of oral glucose tolerance test in patient with schizophrenia.

    Science.gov (United States)

    Margetić, Branimir; Aukst-Margetić, Branka; Badanjak, Anica

    2005-06-01

    We describe the case of a 39-year-old patient with schizophrenia who developed worsening of glucose metabolism during treatment with two different atypical antipsychotics, clozapine and quetiapine. Diabetes mellitus was recognized during clozapine treatment. During quetiapine treatment, while patient was taking diabetic diet, fasting and 1-hour glucose levels and body mass index, decreased, but 2-hour glucose levels increased. This suggests that, in some patients, monitoring of only fasting glucose level and body mass index may be insufficient for detecting the glucose metabolism abnormalities. In those patients oral glucose tolerance test may be recommended. Recommendations about when and how often clinicians should administer the test do not exist in current guidelines. Further studies are needed for the elucidation of this question.

  13. Safety and tolerability of an oral zonisamide loading dose.

    Science.gov (United States)

    Jongeling, Amy C; Richins, Rachel J; Bazil, Carl W

    2015-11-01

    There are a limited number of anticonvulsant medications that can be administered with an oral loading dose in order to rapidly achieve an effective serum level, and most of these have associated adverse effects. Zonisamide is approved for the treatment of partial onset epilepsy, and is used in practice for both generalized and partial onset epilepsy. It is generally well-tolerated, has a long half-life, and can be administered once daily. Unfortunately, the recommended titration schedule for initiating therapy takes several weeks to reach target dose and therapeutic serum levels. We initiated zonisamide therapy using a large initial dose of zonisamide in 32 patients in our epilepsy monitoring unit over the past four years. Adverse effects were rare and involved nausea/vomiting (9.4%) or drowsiness (6.3%). In patients where serum levels were available for review, therapeutic or near-therapeutic levels were achieved after an oral load of 600-900 mg given as divided doses over a 6-12h period. This report is the first to suggest a method of rapidly initiating zonisamide therapy, achieving therapeutic serum levels in a shorter time frame, with an adverse effect profile similar to the recommended titration schedule. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Prophylaxis and therapy of allergy by mucosal tolerance induction with recombinant allergens or allergen constructs.

    Science.gov (United States)

    Wiedermann, Ursula

    2005-10-01

    The mucosal immune system, present along the respiratory, gastrointestinal and genitourinary tract, has to discriminate between harmful pathogens and innocuous antigens, such as food, airborne antigens or the commensal bacterial flora. Therefore the mucosal immune system has acquired two opposing immunological functions, i.e. the induction of immunity and defence of mucosal pathogens, and the induction and maintenance of tolerance to environmental antigens and bacterial flora. As described for autoimmunity a breakdown or failure of tolerance induction is believed to lead also to allergies and food enteropathies. Based on the physiological role to prevent hypersensitivity reactions, tolerance induction via the mucosa has been proposed as a treatment strategy against inflammatory diseases, such as allergies. The aim of our research is to develop mucosal allergy vaccines based on the induction of mucosal tolerance and/or the induction of counter-regulatory immune responses with or without the use of certain mucosal antigen delivery systems, such as lactic acid bacteria. The use of recombinant allergens instead of allergen extracts with varying allergen content and composition may be essential for improvement of the treatment efficacy. In the present review we give examples of different animal models of type I allergy/asthma. Using these models we demonstrate that recombinant allergens or hypoallergenic variants thereof can be successfully used to induce mucosal tolerance in a prophylactic as well as a therapeutic treatment regime. That the concept of mucosal tolerance induction/mucosal vaccine delivery may in principal also function in humans is supported by recent clinical trials with locally (sublingual) applied immunotherapy.

  15. Oral Delivery of a Novel Recombinant Streptococcus mitis Vector Elicits Robust Vaccine Antigen-Specific Oral Mucosal and Systemic Antibody Responses and T Cell Tolerance.

    Directory of Open Access Journals (Sweden)

    Emily Xie

    Full Text Available The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.

  16. Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression.

    LENUS (Irish Health Repository)

    Wang, Jiang Huai

    2012-02-03

    Tolerance to bacterial cell wall components including lipopolysaccharide (LPS) may represent an essential regulatory mechanism during bacterial infection. Two members of the Toll-like receptor (TLR) family, TLR2 and TLR4, recognize the specific pattern of bacterial cell wall components. TLR4 has been found to be responsible for LPS tolerance. However, the role of TLR2 in bacterial lipoprotein (BLP) tolerance and LPS tolerance is unclear. Pretreatment of human THP-1 monocytic cells with a synthetic bacterial lipopeptide induced tolerance to a second BLP challenge with diminished tumor necrosis factor-alpha and interleukin-6 production, termed BLP tolerance. Furthermore, BLP-tolerized THP-1 cells no longer responded to LPS stimulation, indicating a cross-tolerance to LPS. Induction of BLP tolerance was CD14-independent, as THP-1 cells that lack membrane-bound CD14 developed tolerance both in serum-free conditions and in the presence of a specific CD14 blocking monoclonal antibody (MEM-18). Pre-exposure of THP-1 cells to BLP suppressed mitogen-activated protein kinase phosphorylation and nuclear factor-kappaB activation in response to subsequent BLP and LPS stimulation, which is comparable with that found in LPS-tolerized cells, indicating that BLP tolerance and LPS tolerance may share similar intracellular pathways. However, BLP strongly enhanced TLR2 expression in non-tolerized THP-1 cells, whereas LPS stimulation had no effect. Furthermore, a specific TLR2 blocking monoclonal antibody (2392) attenuated BLP-induced, but not LPS-induced, tumor necrosis factor-alpha and interleukin-6 production, indicating BLP rather than LPS as a ligand for TLR2 engagement and activation. More importantly, pretreatment of THP-1 cells with BLP strongly inhibited TLR2 activation in response to subsequent BLP stimulation. In contrast, LPS tolerance did not prevent BLP-induced TLR2 overexpression. These results demonstrate that BLP tolerance develops through down-regulation of TLR2

  17. Immune tolerance induction in hemophilia A: a review.

    Science.gov (United States)

    Mariani, Guglielmo; Siragusa, Sergio; Kroner, Barbara L

    2003-02-01

    In this article, a comparative analysis of the data stemming from the studies conducted in the field of immune tolerance treatment (ITT) of hemophilia A was attempted. Comparisons are difficult because previous studies differ in many respects, including the dosage of factor (F) VIII, the number of FVIII administrations per day, the association with immunosuppressive drugs (prednisone, cyclophosphamide), and, most importantly, the definition of success in terms of the reacquisition of tolerance. However, a number of variables consistently influenced outcome: the inhibitor titer, either the maximum one or the one assayed before immune tolerance (IT) start and age. As to the FVIII dose, results are contrasting, even though the overall impression is that high dosages are associated with higher success rates. Treatment duration analyses appear to be fairly consistent in all the studies, with 1 year as the crucial time period useful in predicting outcome. Preliminary data suggest that concentrates containing von Willebrand factor may increase the success rate and allow patients refractory to IT procedures carried out with ultrapure or recombinant concentrates to become tolerant in the end. These data need to be formally confirmed in trials that compare the different brands. In the studies published so far, a common language and widely accepted definitions of the variables have emerged, which are important in setting up the controlled trials and improving the comparison among published data.

  18. Thymic CCL2 influences induction of T-cell tolerance

    DEFF Research Database (Denmark)

    Cédile, O; Løbner, M; Toft-Hansen, H

    2014-01-01

    Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell development by controlling the selection of the T cell receptor repertoire. DC have been described to take up antigens in the periphery and migrate into the thymus where they mediate tolerance via deletion of autoreactiv...

  19. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Pedersen, Bente K;

    2014-01-01

    We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty-four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age......: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m(2), P > 0.05) underwent a 180-min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6-(2)H2]glucose and ingestion of [U-(13)C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials......, plasma glucose concentrations and kinetics, insulin, C-peptide, and glucagon were measured. Rates (mg kg(-1) min(-1)) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; Ra OGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, Ra...

  20. Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

    Directory of Open Access Journals (Sweden)

    Philippe Moingeon

    2012-01-01

    Full Text Available The clinical efficacy of sublingual immunotherapy (SLIT with natural allergen extracts has been established in IgE-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. Sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. The oral immune system comprises various antigen-presenting cells, including Langerhans cells, as well as myeloid and plasmacytoid dendritic cells (DCs with a distinct localisation in the mucosa, along the lamina propria and in subepithelial tissues, respectively. In the absence of danger signals, all these DC subsets are tolerogenic in that they support the differentiation of Th1- and IL10-producing regulatory CD4+ T cells. Oral tissues contain limited numbers of mast cells and eosinophils, mostly located in submucosal areas, thereby explaining the good safety profile of SLIT. Resident oral Th1, Th2, and Th17 CD4+ T cells are located along the lamina propria, likely representing a defence mechanism against infectious pathogens. Second-generation sublingual vaccines are being developed, based upon recombinant allergens expressed in a native conformation, possibly formulated with Th1/T reg adjuvants and/or mucoadhesive particulate vector systems specifically designed to target oral dendritic cells.

  1. Robust Adaptive Fault-Tolerant Tracking Control of Three-Phase Induction Motor

    Directory of Open Access Journals (Sweden)

    Hossein Tohidi

    2014-01-01

    Full Text Available This paper deals with the problem of induction motor tracking control against actuator faults and external disturbances using the linear matrix inequalities (LMIs method and the adaptive method. A direct adaptive fault-tolerant tracking controller design method is developed based on Lyapunov stability theory and a constructive algorithm based on linear matrix inequalities for online tuning of adaptive and state feedback gains to stabilize the closed-loop system in order to reduce the fault effect with disturbance attenuation. Simulation results reveal the merits of proposed robust adaptive fault-tolerant tracking control scheme on an induction motor subjected to actuator faults.

  2. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

    Directory of Open Access Journals (Sweden)

    Yi-Bin Chen

    2016-01-01

    Full Text Available The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable.

  3. Tolerance Induction of Horse Allergy by Horse Contact with Curly Horses.

    Science.gov (United States)

    Mitlehner, W; Mitlehner, H C

    2017-07-01

    A horse allergic rider completed 60 riding lessons on Curly Horses within six months. This rider has become clinically tolerant to normal horse breeds within this time. This case may indicate that riding and brushing ABCR Curly Horses after 60 riding hours facilitates tolerance induction. Our data indicate that this could be a valid alternative to the common recommendation to strictly avoid horse riding. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Heated Allergens and Induction of Tolerance in Food Allergic Children

    Directory of Open Access Journals (Sweden)

    Irmeli Penttila

    2013-06-01

    Full Text Available Food allergies are one of the first manifestations of allergic disease and have been shown to significantly impact on general health perception, parental emotional distress and family activities. It is estimated that in the Western world, almost one in ten children have an IgE-mediated allergy. Cow’s milk and egg allergy are common childhood allergies. Until recently, children with food allergy were advised to avoid all dietary exposure to the allergen to which they were sensitive, in the thought that consumption would exacerbate their allergy. However, recent publications indicate that up to 70% of children with egg allergy can tolerate egg baked in a cake or muffin without apparent reaction. Likewise, up to 75% of children can tolerate baked goods containing cow’s milk, and these children demonstrate IgE and IgG4 profiles indicative of tolerance development. This article will review the current literature regarding the use of heated food allergens as immunotherapy for children with cow’s milk and egg allergy.

  5. Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

    OpenAIRE

    Philippe Moingeon; Laurent Mascarell

    2012-01-01

    The clinical efficacy of sublingual immunotherapy (SLIT) with natural allergen extracts has been established in IgE-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. Sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. The oral immune system comprises various antigen-presenting cells, including Langerhans cells, as well as myeloid and plasmacytoid dendritic cells (DCs) with...

  6. Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance

    Directory of Open Access Journals (Sweden)

    Loosbroock C

    2014-12-01

    Full Text Available Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gram-negative bacterial outer membrane antigen lipopolysaccharide (LPS. TNF-α is responsible for altering vascular permeability and activating infiltrating inflammatory cells, such as monocytes and neutrophils. Interestingly, TNF-α has also demonstrated the ability to induce tolerance to subsequent challenges with TNF-α or LPS in monocyte and macrophage cell populations. Tolerance is characterized by the inability to mount a typical inflammatory response during subsequent challenges following the initial exposure to an inflammatory mediator such as LPS. The ability of TNF-α to induce a tolerant-like state with regard to LPS is most likely a regulatory mechanism to prevent excessive inflammation. We hypothesized that the induction of tolerance or the degree of tolerance is dependent upon the production of TNF-α during the primary response to LPS. To investigate TNF-α-dependent tolerance, human monocytic THP-1 cells were treated with TNF-α-neutralizing antibodies or antagonistic TNF-α receptor antibodies before primary LPS stimulation and then monitored for the production of TNF-α during the primary and challenge stimulation. During the primary stimulation, anti-TNF-α treatment effectively attenuated the production of TNF-α and interleukin-1β; however, this reduced production did not impact the induction of endotoxin tolerance. These results demonstrate that interfering with TNF-α signaling attenuates production of inflammatory cytokines without affecting the induction of tolerance. Keywords: endotoxin tolerance, lipopolysaccharide, tumor necrosis factor-alpha, anti-tumor necrosis factor-alpha, THP-1 cells

  7. Oxytocin and oral misoprostol for labor induction in prelabor rupture of membranes

    Directory of Open Access Journals (Sweden)

    Rashmi

    2016-02-01

    Conclusions: Although oxytocin resulted in shorter induction to delivery interval, oral misoprostol is still an effective option for PROM, as delivery and neonatal outcomes were similar. [Int J Reprod Contracept Obstet Gynecol 2016; 5(2.000: 379-383

  8. Induction of nitrate tolerance is not a useful treatment in cluster headache

    DEFF Research Database (Denmark)

    Christiansen, I; Iversen, Helle Klingenberg; Olesen, J

    2000-01-01

    UNLABELLED: The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate-induced headache to the vascular adaptation during continuous nitrate adm...... be taken into consideration....

  9. The Induction and Maintenance of Transplant Tolerance Engages Both Regulatory and Anergic CD4+ T cells

    Science.gov (United States)

    Besançon, Alix; Baas, Marije; Goncalves, Tania; Valette, Fabrice; Waldmann, Herman; Chatenoud, Lucienne; You, Sylvaine

    2017-01-01

    Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3+ regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8+ T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4+ T cells in tolerization by CD3 antibodies. We show that both Foxp3+ Tregs and CD4+ T cell anergy play a role in the induction of tolerance and its maintenance. Foxp3+ Tregs resisted CD3 antibody-mediated depletion, unlike intragraft Th1 CD4+ lymphocytes coexpressing granzyme B and Tbx21, which were selectively eliminated. Tregs were mandatory for induction of tolerance as their depletion at the time of CD3 antibody therapy or for a short time thereafter, by an antibody to CD25 (PC61), led to graft rejection. Early treatment with CTLA-4 antibody gave the same outcome. In contrast, neither PC61 nor anti-CTLA-4 given late, at day 100 posttransplant, reversed tolerance once established. Ablation of Foxp3 T cells after diphtheria toxin injection in tolerant Foxp3DTR recipient mice provided the same outcome. Alloreactive T cells had been rendered intrinsically unresponsive as total CD4+ or Treg-deprived CD4+ T cells from tolerant recipients were unable to mount donor-specific IFN-γ responses. In addition, intragraft Treg-deprived CD4+ T cells lacked proliferative capacities, expressed high levels of the inhibitory receptor PD-1, and exhibited a CD73hiFR4hi phenotype, thus reflecting a state of T cell anergy. We conclude that Tregs play a substantive and critical role in guiding the immune system toward tolerance of the allograft, when induced by CD3 antibody, but are less important for maintenance of the tolerant state, where T cell anergy appears sufficient.

  10. The Induction and Maintenance of Transplant Tolerance Engages Both Regulatory and Anergic CD4(+) T cells.

    Science.gov (United States)

    Besançon, Alix; Baas, Marije; Goncalves, Tania; Valette, Fabrice; Waldmann, Herman; Chatenoud, Lucienne; You, Sylvaine

    2017-01-01

    Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance. Foxp3(+) Tregs resisted CD3 antibody-mediated depletion, unlike intragraft Th1 CD4(+) lymphocytes coexpressing granzyme B and Tbx21, which were selectively eliminated. Tregs were mandatory for induction of tolerance as their depletion at the time of CD3 antibody therapy or for a short time thereafter, by an antibody to CD25 (PC61), led to graft rejection. Early treatment with CTLA-4 antibody gave the same outcome. In contrast, neither PC61 nor anti-CTLA-4 given late, at day 100 posttransplant, reversed tolerance once established. Ablation of Foxp3 T cells after diphtheria toxin injection in tolerant Foxp3(DTR) recipient mice provided the same outcome. Alloreactive T cells had been rendered intrinsically unresponsive as total CD4(+) or Treg-deprived CD4(+) T cells from tolerant recipients were unable to mount donor-specific IFN-γ responses. In addition, intragraft Treg-deprived CD4(+) T cells lacked proliferative capacities, expressed high levels of the inhibitory receptor PD-1, and exhibited a CD73(hi)FR4(hi) phenotype, thus reflecting a state of T cell anergy. We conclude that Tregs play a substantive and critical role in guiding the immune system toward tolerance of the allograft, when induced by CD3 antibody, but are less important for maintenance of the tolerant state, where T cell anergy appears sufficient.

  11. Studies of tolerance induction through mixed chimerism in cynomolgus monkeys. Method for detection of chimeric cells and effect of thymic irradiation on induction of tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Hoshino, Tomoaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    To establish the method for the detection of chimerism in cynomologus monkeys, we tested cross reactivity of various anti-HLA monoclonal antibodies (mAb) to cynomolgus monkeys. In 29 mAb we tested, only three monoclonal anti-HLA antibodies crossreacted with lymphocytes of monkeys. With these mAb, chimeric cell can be detected up to 1% by flow cytometric analysis (study 1). Utilizing the method we developed in study 1, we applied the regimen that induces mixed chimerism and skin graft tolerance in mice to renal allotransplantation of cynomolgus monkey. Regimen A includes non-lethal dose of total body irradiation (TBI), administration of anti-thymocyte globulin (ATG) for 3 days, donor bone marrow infusion and 45 days course of cyclosporine (CYA) administration. We added 7 Gy of thymic irradiation on day-6 in regimen B and on day-1 in regimen C. Although all monkeys in regimen A and B consistently developed chimerism, they rejected kidney allografts soon after stopping CYA. In contrast, 4 monkeys out of 5 failed to develop chimerism in regimen C, but renal allograft tolerance was induced in one monkey who developed chimerism in regimen C. In conclusion, the induction of chimerism is considered necessary but not sufficient for tolerance induction. (author)

  12. Correlation of oral health of children with acute leukemia during the induction phase

    Directory of Open Access Journals (Sweden)

    Kanchan P. Dholam

    2014-01-01

    Full Text Available Background: Treatment of acute leukemia′s- a common childhood malignancy, involves intensive and powerful multi-drug chemotherapeutic regime. Oral lesions are a common complication in these patients affecting oral health status. Aim: This study was conducted to evaluate and assess the oral health status of newly diagnosed leukemic pediatric patients during induction phase and its correlation to outcome of induction therapy. Material Methods: Oral examinations was done in 33 children between the age group of 5-15 years with acute lymphoblastic leukemia (ALL and acute myloblastic leukemia (AML, who were undergoing chemotherapy. Oral Hygiene Index- Simplified, (OHI-S decayed missing filled teeth index (def/DMFT, Loe and Sillness index for gingiva, and complete blood count at first and fourth week of induction phase were recorded for each patient. The changes in the oral health status were analyzed with Wilcoxon signed rank test. Results: During an induction phase it was observed that level of OHI-S (P = 0.002, Loe and Sillness index (P = 0.003, def/DMFT index (P = 0.076, platelet count (P = 0.00 increased significantly and no significant difference was noted in hemoglobin (P = 0.4 and total leucocytes count (P = 0.11. Conclusion: It was observed that, although oral health status had significantly worsened, the induction outcome was not affected.

  13. Oral tolerance El fenómeno de la tolerancia oral

    Directory of Open Access Journals (Sweden)

    Martín Correa

    1989-03-01

    Full Text Available

    The phenomenon of decreased systemic Immune response to orally administered antigens is known as oral tolerance (OT. Though It was anecdotically described many years ago, the mechanisms and potential applications of OT are still mostly speculative. Specificity and thymus-dependence are among its most remarkable features. OT is manifested by the absence of systemic antibodies, of delayed type hypersensitivity and of proliferate responses toward the specific antigen. Potential mechanisms of OT have been grouped in three types, namely: Immunologic, gastrointestinal and individual. The most Important of the immunologic mechanisms might be the existence of counter-suppressive cells but their intimate functioning has not been thoroughly elucidated. The study of OT opens a wide research field with Implications for the immunoprophylaxis and Immunotherapy of many diseases.

    Se da el nombre de tolerancia oral al estado de respuesta inmune sistémica disminuida a antígenos administrados por la vía oral. Si bien el fenómeno fue descrito anecdóticamente desde hace muchos años, sus mecanismos y posibles aplicaciones todavía son materia de especulación. Entre sus características notables se destacan la especificidad y la timodependencia. La tolerancia se manifiesta por ausencia de anticuerpos sistémicos, de hipersensibilidad de tipo retardado y de respuestas proliferativas al antígeno específico. Los posibles mecanismos responsables de la tolerancia oral se han agrupado en tres tipos: inmunológicos, gastrointestinales e individuales. En cuanto a los inmunológicos, el más importante podría ser la existencia de las células contrasupresoras, pero los mecanismos íntimos de funcionamiento de éstas no están completamente elaborados. El estudio del fenómeno de la tolerancia oral abre un amplio campo

  14. Comparative Study of Oral and Vaginal Misoprostol for Induction of Labour, Maternal and Foetal Outcome

    OpenAIRE

    Komala, Kambhampati; Reddy, Meherlatha; Quadri, Iqbal Jehan; B., Suneetha; V., Ramya

    2013-01-01

    Background: Misoprostol is a new promising agent for cervical ripening and induction of labour .The ideal dose, route and frequency of administration of misoprostol are still under investigation. Although, vaginal application of misoprostol has been validated as a reasonable mean of induction, there is a patient resistance to digital examination and there is a risk of ascending infection. For this reason, oral administration of misoprostol for cervical ripening and labour induction has been t...

  15. Tolerance induction to human stem cell transplants with extension to their differentiated progeny.

    Science.gov (United States)

    Lui, Kathy O; Howie, Duncan; Ng, Shu-Wing; Liu, Shubai; Chien, Kenneth R; Waldmann, Herman

    2014-12-01

    There is increasing interest in transplantation of human stem cells for therapeutic purposes. It would benefit future application if one could achieve their long-term acceptance and functional differentiation in allogeneic hosts using minimal immunosuppression. Allogeneic stem cell transplants differ from conventional tissue transplants insofar as not all alloantigens are revealed during tolerance induction. This risks that the immune system tolerized to antigens expressed by progenitors may still remain responsive to antigens expressed later during differentiation. Here we show that brief induction with monoclonal antibody-mediated coreceptor and costimulation blockade enables long-term engraftment and tolerance towards murine ESCs, hESCs, human induced pluripotent stem cells (iPSCs) and hESC-derived progenitors in outbred murine recipients. Tolerance induced to PSC-derived progenitors extends to their differentiated progenies, and sometimes even to different tissues derived from the same donor. Global gene expression profiling identifies clear features in T cells from tolerized grafts that are distinct from those involved in rejection.

  16. Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction

    Institute of Scientific and Technical Information of China (English)

    Mony Shuvy; Tiberiu Hershcovici; Cristina Lull-Noguera; Harry Wichers; Ofer Danay; Dan Levanon; Lidya Zolotarov; Yaron Ilan

    2008-01-01

    AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.METHODS: Four groups of mice were studied.Colitis was induced by intracolonic instillation of TNBS in groups A and B.Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin.Mice were evaluated for development of macroscopic and microscopic.The immune effects of Shiitakke were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay.RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by significant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively).This beneficial effect was associated with a significant increase in the intrahepatic CD8+ lymphocyte trapping,demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio.These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells.A similar effect was observed when Shiitake was administered to animals without disease induction.CONCLUSION: Shiitake extract affected livermediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.

  17. IL-10 and IL-27 producing dendritic cells capable of enhancing IL-10 production of T cells are induced in oral tolerance.

    Science.gov (United States)

    Shiokawa, Aya; Tanabe, Kosuke; Tsuji, Noriko M; Sato, Ryuichiro; Hachimura, Satoshi

    2009-06-30

    Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to ingested antigens (Ag). Dendritic cells (DC) have been revealed as important immune regulators, however, the precise role of DC in oral tolerance induction remains unclear. We investigated the characteristics of DC in spleen, mesenteric lymph node (MLN), and Peyer's patch (PP) after oral Ag administration in a TCR-transgenic mouse model. DC from PP and MLN of tolerized mice induced IL-10 production but not Foxp3 expression in cocultured T cells. IL-10 production was markedly increased after 5-7-day Ag administration especially in PP DC. On the other hand, IL-27 production was increased after 2-5-day Ag administration. CD11b(+) DC, which increased after ingestion of Ag, prominently expressed IL-10 and IL-27 compared with CD11b(-) DC. These results suggest that IL-10 and IL-27 producing DC are increased by interaction with antigen specific T cells in PP, and these DC act as an inducer of IL-10 producing T cells in oral tolerance.

  18. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    -induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...... possibility that l-arginine-based nutritional and/or pharmaceutical therapies may benefit glucose tolerance by improving the postprandial GLP-1 response in obese individuals....

  19. Fault-tolerant Control of Inverter-fed Induction Motor Drives

    DEFF Research Database (Denmark)

    Thybo, C.

    The main purpose of this work was to investigate how fault-tolerant control (FTC) could be included in the control scheme of frequency converter fed induction motor applications. This was approached by identifying the potential failure modes for which fault tolerant control should be applied...... a current sensor fault, by switching to a closed loop scalar controller, was analysed. The main contributions of this work are · An investigation of the potential failure modes of inverter fed induction motor drives. · An extension of the FTC development cycle, to include economical cost-benefit analysis....... A description of the different frequency converter components, including models of the inverter, sensors and controllers was given, followed by a fault mode and effect analysis, which points out the potential fault modes of the design. Among the listed fault modes, two were found to be of particular practical...

  20. Fault-tolerant Control of Inverter-fed Induction Motor Drives

    DEFF Research Database (Denmark)

    Thybo, C.

    The main purpose of this work was to investigate how fault-tolerant control (FTC) could be included in the control scheme of frequency converter fed induction motor applications. This was approached by identifying the potential failure modes for which fault tolerant control should be applied...... a current sensor fault, by switching to a closed loop scalar controller, was analysed. The main contributions of this work are · An investigation of the potential failure modes of inverter fed induction motor drives. · An extension of the FTC development cycle, to include economical cost-benefit analysis....... A description of the different frequency converter components, including models of the inverter, sensors and controllers was given, followed by a fault mode and effect analysis, which points out the potential fault modes of the design. Among the listed fault modes, two were found to be of particular practical...

  1. Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells.

    Directory of Open Access Journals (Sweden)

    Nicole Bacher

    Full Text Available BACKGROUND: Administration of interferon-α (IFN-α represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC that are known to induce anergic regulatory T cells (iTregs. METHODOLOGY/PRINCIPAL FINDINGS: IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an increased capacity of DC to stimulate T cell activation compared to control tolerogenic DC. We observed a strengthened T cell proliferation and increased IFN-γ production of CD4(+ and CD8(+ T cells stimulated by IFN-α-DC, demonstrating a restoration of the immunogenic capacity of tolerogenic DC in the presence of IFN-α. Notably, restimulation experiments revealed that IFN-α treatment of tolerogenic DC abolished the induction of T cell anergy and suppressor function of iTregs. In contrast, IFN-α neither affected the priming of iTregs nor converted iTregs into effector T cells. CONCLUSIONS/SIGNIFICANCE: IFN-α inhibits the induction of T cell tolerance by reversing the tolerogenic function of human DC.

  2. Induction of thymic tolerance as possibility in prevention of recurrent spontaneous abortion.

    Science.gov (United States)

    Bubanovic, I V

    2003-04-01

    A major process through which the immune system becomes tolerant to self-proteins involves the deletion of self-reactive cells in the thymus and/or inhibition of specific Th(1) cells clones. Deletion process includes two selection mechanisms in which the thymus eliminates unwanted thymocytes are known as positive selection and negative selection. The thymus is an antigenically privileged site, mainly for it is discrete by blood-thymus barrier. Many researches were shown that intrathymic inoculation of any antigen resulted in specific tolerance induction. The embryo/fetus and placenta are an allograft to which the mother must remain immunologically tolerant in order for the fetus to survive. Today, there is much interest focused on the immunology of recurrent spontaneous abortion (RSA). Up to 50% of RSA may be mediated by the immune system via inadequate maternal anti-paternal response. Nature of this maternal-fetal disturbance represents disbalance in Th(1)/Th(2) activity. Contra-shift in Th(1)/Th(2) activity is the basis for immunotherapy with paternal leukocyte immunization (PLI). PLI induce some kind of peripheral tolerance on embryonic/fetal/trophoblast antigens, but problems of central tolerance are still open. Intrathymic inoculation of fetal or paternal cells (like leukocyte, thymic dendritic cells, trophoblast cells) or paternal set of MHC molecules may cause central specific tolerance and may be a new possibility for immunotherapy in RSA patients.

  3. Recipients with In Utero Induction of Tolerance Upregulated MHC Class I in the Engrafted Donor Skin

    Directory of Open Access Journals (Sweden)

    Jeng-Chang Chen

    2014-01-01

    Full Text Available The alterations in MHC class I expression play a crucial step in immune evasion of cancer or virus-infected cells. This study aimed to examine whether tolerized grafts modified MHC class I expression. FVB/N mice were rendered tolerant of C57BL/6 alloantigens by in utero transplantation of C57BL/6 marrows. Postnatally, engrafted donor skins and leukocytes were examined for their MHC expression by quantitative real-time PCR and flow cytometry. Engrafted donor skins upregulated their MHC class I related gene transcripts after short-term (1~2 weeks or long-term (>1 month engraftment. This biological phenomenon was simultaneously associated with upregulation of TAP1 gene transcripts, suggesting an important role of TAP1 in the regulation of MHC class I pathway. The surface MHC class I molecules of H-2Kb in engrafted donor leukocytes consistently showed overexpression. Conclusively, the induction of allograft tolerance involved biological modifications of donor transplants. The overexpression of MHC class I within engrafted transplants of tolerant mice might be used as the tolerance biomarkers for identifying a state of graft tolerance.

  4. Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Judith Prado

    Full Text Available CONTEXT AND OBJECTIVE: Dipyrone is a widely used over-the-counter antipyretic in Latin America, and elsewhere among Latin immigrants. Despite limited evidence, physicians often prescribe oral ibuprofen or intramuscular dipyrone as the most effective antipyretics. Our aim was to compare the antipyretic efficacy and tolerability of a single dose of oral ibuprofen, oral dipyrone or intramuscular dipyrone in febrile children. DESIGN AND SETTING: Randomized, single-blind clinical trial, at San Bartolomé Mother-Child National Teaching Hospital, Lima, Peru. METHODS: Children from six months to six years old with fever (rectal temperature: 38.3 to 39.8° C in the emergency ward between February and June 2003 were eligible. Seventy-five children were randomly assigned to receive a single dose of oral ibuprofen (10 mg/kg, oral dipyrone (15 mg/kg or intramuscular dipyrone (15 mg/kg. The primary outcome was mean temperature reduction after 30, 45, 60, 90 and 120 minutes. Secondary outcomes were fever-associated symptoms and clinical adverse events. RESULTS: Fever decreased by about 0.5° C after 45 minutes and by about 1.0° C after 120 minutes in all three groups. Mean temperatures were similar for the three groups at all times. There was a significant decrease in fever-associated symptoms for all groups. Six patients (four receiving oral dipyrone and two receiving ibuprofen were withdrawn because of vomiting within 20 minutes after first dose of study medication. One patient assigned to oral ibuprofen presented transient urticaria. CONCLUSIONS: Antipyretic efficacy and tolerability were similar for oral ibuprofen, oral dipyrone and intramuscular dipyrone. Oral antipyretics seem more appropriate for feverish children.

  5. Nod2 suppresses Borrelia burgdorferi mediated murine Lyme arthritis and carditis through the induction of tolerance.

    Directory of Open Access Journals (Sweden)

    Tanja Petnicki-Ocwieja

    Full Text Available The internalization of Borrelia burgdorferi, the causative agent of Lyme disease, by phagocytes is essential for an effective activation of the immune response to this pathogen. The intracellular, cytosolic receptor Nod2 has been shown to play varying roles in either enhancing or attenuating inflammation in response to different infectious agents. We examined the role of Nod2 in responses to B. burgdorferi. In vitro stimulation of Nod2 deficient bone marrow derived macrophages (BMDM resulted in decreased induction of multiple cytokines, interferons and interferon regulated genes compared with wild-type cells. However, B. burgdorferi infection of Nod2 deficient mice resulted in increased rather than decreased arthritis and carditis compared to control mice. We explored multiple potential mechanisms for the paradoxical response in in vivo versus in vitro systems and found that prolonged stimulation with a Nod2 ligand, muramyl dipeptide (MDP, resulted in tolerance to stimulation by B. burgdorferi. This tolerance was lost with stimulation of Nod2 deficient cells that cannot respond to MDP. Cytokine patterns in the tolerance model closely paralleled cytokine profiles in infected Nod2 deficient mice. We propose a model where Nod2 has an enhancing role in activating inflammation in early infection, but moderates inflammation after prolonged exposure to the organism through induction of tolerance.

  6. Tolerance induction in hemophilia A animal models: battling inhibitors with antigen-specific immunotherapies.

    Science.gov (United States)

    Adair, Patrick; Su, Yan; Scott, David W

    2013-05-01

    Hemophilia A is an X-linked recessive bleeding disorder due to either a lack of or greatly reduced activity in the blood coagulation protein factor VIII (FVIII), due to mutations in the F8 gene. This poses significant challenges for FVIII replacement therapy since hemophilic patients are not immunologically tolerant to the protein. Thus, a proportion of patients who receive plasma-derived or recombinant FVIII replacement therapy develop anti FVIII neutralizing antibodies, known as "inhibitors." These patients require long-term regimens of high dose FVIII administration, which has varying success rates and prohibitive costs. Therefore, therapeutics for tolerance induction in such patients with inhibitors are desired. In this review, we address the current progress of immunotherapies for inducing FVIII specific tolerance in animal models of hemophilia A. Specifically we discuss the beneficial effects of B-cell depletion on immune tolerance induction (ITI), B-cell mediated gene therapy, antigen-coupled lymphocyte therapy, and regulatory T-cell epitopes (Tregitopes).

  7. Titrated oral misoprostol solution compared with oxytocin for induction of labor in women with unfavorable cervix

    Directory of Open Access Journals (Sweden)

    Akrami M

    2011-10-01

    Full Text Available "nBackground: Uterine contractions and an appropriate cervix are two important factors in labor contributing to good pregnancy outcomes. Oxytocin and prostaglandins, such as misoprostol, are used for the induction of labor. Misoprostol is used for cervical ripening and labor induction. The aim of this trial was to compare the efficacy and safety of titrated oral misoprostol solution with oxytocin for labor induction in pregnant women with an unfavorable cervix."n "nMethods: In this randomized double-blind clinical trial, 140 women with a gestational age of 34-42 weeks and an unfavorable cervix were recruited. The participants had an indication for labor induction and had been referred to the Women's Hospital in Tehran, Iran between January 2010 and January 2011. The participants were randomly assigned to receive 20 µg/hour titrated oral misoprostol plus intravenous placebo or 6 mU/min oxytocin plus oral placebo. In case contractions were inadequate, the drug doses were gradually increased. Pharmacological complications, the mean interval from the start of induction till vaginal delivery and delivery type were monitored and analyzed in both groups."n "nResults: The mean interval from the start of induction till vaginal delivery in misoprostol group was shorter than the oxytocin group (11.07±3.42 vs. 14.87±3.21 hours, P=0.001. The frequency of pharmacological complications and vaginal or cesarean deliveries were similar between the two groups (P>0.05."n "nConclusion: Use of titrated oral misoprostol is a safe and effective method for labor induction in pregnant women with unfavorable cervix. Misoprostol is associated with a shorter interval from induction to vaginal delivery than oxytocin.

  8. Induction chemotherapy for oral cavity cancer patients: Current status and future perspectives.

    Science.gov (United States)

    Marta, Gustavo Nader; William, William N; Feher, Olavo; Carvalho, André Lopes; Kowalski, Luiz Paulo

    2015-12-01

    There is a lack of data from phase III randomized studies to support an ideal approach for locally advanced oral cavity cancer patients. In general, surgery, radiotherapy and chemotherapy are valid treatment options, and combined approach is usually indicated given poor clinical outcomes with single modality therapy. The aim of this study is to review the current status and future perspectives of induction chemotherapy for locally advanced oral cavity cancer patients.

  9. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

    DEFF Research Database (Denmark)

    Hulman, Adam; Simmons, Rebecca Kate; Vistisen, Dorte

    2017-01-01

    We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies...... in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different...... patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak...

  10. Myeloid-derived suppressor cells mediate tolerance induction in autoimmune disease.

    Science.gov (United States)

    Wegner, Anja; Verhagen, Johan; Wraith, David C

    2017-01-31

    In multiple sclerosis (MS) T cells aberrantly recognize self-peptides of the myelin sheath and attack the central nervous system (CNS). Antigen-specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non-specific immunosuppressive drugs, is a promising approach to combat autoimmune disease, but the cellular mechanisms behind successful therapy remain poorly understood. Myeloid-derived suppressor cells (MDSCs) have been studied intensively in the field of cancer and to a lesser extent in autoimmunity. Because of their suppressive effect on the immune system in cancer, we hypothesized that the development of MDSCs and their interaction with CD4(+) T cells could be beneficial for antigen-specific immunotherapy. Hence, changes in the quantity, phenotype and function of MDSCs during tolerance induction in our model of MS were evaluated. We reveal, for the first time, an involvement of a subset of MDSCs, known as polymorphonuclear (PMN)-MDSCs, in the process of tolerance induction. PMN-MDSCs were shown to adopt a more suppressive phenotype during peptide immunotherapy and inhibit CD4(+) T-cell proliferation in a cell-contact-dependent manner, mediated by arginase-1. Moreover, increased numbers of tolerogenic PMN-MDSCs, such as observed over the course of peptide immunotherapy, were demonstrated to provide protection from disease in a model of experimental autoimmune encephalomyelitis.

  11. Role of titrated low dose oral misoprostol solution in induction of labour

    Directory of Open Access Journals (Sweden)

    Sarvottma Antil

    2016-03-01

    Conclusions: For induction of labour in women with term gestation after cervical priming, low dose oral misoprostol solution in titrated doses and intravenous oxytocin were found to be comparable with each other in terms of labour outcomes, efficacy and adverse effects. [Int J Reprod Contracept Obstet Gynecol 2016; 5(3.000: 775-782

  12. Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

    OpenAIRE

    1990-01-01

    The development of safe methods for inducing donor-specific tolerance across xenogeneic barriers could potentially relieve the critical shortage of allograft donors that currently limits the applicability of organ transplantation. We report here that such tolerance can be induced in a xenogeneic combination (rat----mouse) using a nonmyeloablative and nonlethal preparative regimen. Successful induction of chimerism and donor-specific transplantation tolerance required pretreatment of recipient...

  13. Orally administered misoprostol for induction of labor with prelabor rupture of membranes at term.

    Science.gov (United States)

    Radoff, Kari A

    2014-01-01

    Prelabor rupture of membranes (PROM) occurs in approximately 8% to 10% of women with term pregnancies. The management of PROM continues to be controversial. Approaches include expectant management and immediate induction of labor. The use of orally administered misoprostol for the management of women with PROM may provide significant advantages when they choose immediate induction of labor. This literature review presents current evidence that supports the use of oral misoprostol for women with PROM, including the benefits of a decreased interval time from PROM to vaginal birth, good safety profile, and reductions in the use of oxytocin augmentation and epidural anesthesia. In addition to clinically proven benefits to women of oral misoprostol for PROM, it also has the potential to reduce chorioamnionitis by reducing the number of sterile vaginal examinations performed thereby reducing the risk of ascending bacteria. Women have also reported acceptability and satisfaction when using oral misoprostol for immediate induction of labor. This review of literature discusses what is known about the use of orally administered misoprostol for the management of term PROM and makes recommendations for clinical use.

  14. Tolerance induction using nanoparticles bearing HY peptides in bone marrow transplantation.

    Science.gov (United States)

    Hlavaty, Kelan A; McCarthy, Derrick P; Saito, Eiji; Yap, Woon Teck; Miller, Stephen D; Shea, Lonnie D

    2016-01-01

    Allogeneic cell therapies have either proven effective or have great potential in numerous applications, though the required systemic, life-long immunosuppression presents significant health risks. Inducing tolerance to allogeneic cells offers the potential to reduce or eliminate chronic immunosuppression. Herein, we investigated antigen-loaded nanoparticles for their ability to promote transplant tolerance in the minor histocompatibility antigen sex-mismatched C57BL/6 model of bone marrow transplantation. In this model, the peptide antigens Dby and Uty mediate rejection of male bone marrow transplants by female CD4+ and CD8+ T cells, respectively, and we investigated the action of nanoparticles on these T cell subsets. Antigens were coupled to or encapsulated within poly(lactide-co-glycolide) (PLG) nanoparticles with an approximate diameter of 500 nm. Delivery of the CD4-encoded Dby epitope either coupled to or encapsulated within PLG particles prevented transplant rejection, promoted donor-host chimerism, and suppressed proliferative and IFN-γ responses in tolerized recipients. Nanoparticles modified with the Uty peptide did not induce tolerance. The dosing regimen was investigated with Dby coupled particles, and a single dose delivered the day after bone marrow transplant was sufficient for tolerance induction. The engraftment of cells was significantly affected by PD-1/PDL-1 costimluation, as blockade of PD-1 reduced engraftment by ∼50%. In contrast, blockade of regulatory T cells did not impact the level of chimerism. The delivery of antigen on PLG nanoparticles promoted long-term engraftment of bone marrow in a model with a minor antigen mismatch in the absence of immunosuppression, and this represents a promising platform for developing a translatable, donor-specific tolerance strategy.

  15. The immune tolerance induction (ITI) dose debate: does the International ITI Study provide a clearer picture?

    Science.gov (United States)

    Ettingshausen, C Escuriola; Kreuz, W

    2013-01-01

    Among the proposed predictors for immune tolerance induction (ITI) outcome, the therapeutic regimen - specifically the dose and frequency of administered factor VIII (FVIII) as well as FVIII product type - is intensely debated. Are there any advantages for low-dose regimens (50 IU FVIII kg(-1) three times a week) over high-dose regimens (200 IU FVIII kg day(-1)) or vice versa? Are von Willebrand factor (VWF)-containing plasma-derived concentrates superior to recombinant FVIII concentrates for tolerance induction? A review of the available literature indicates that patients with good prognostic factors can achieve success with either low-dose or high-dose ITI regimens. Retrospective data suggest that patient characteristics such as maximum historical inhibitor titres and pre-ITI inhibitor titres are better predictors of treatment success than dose. Results of the prospective International ITI Study have recently become available. In inhibitor patients with good prognosis, success rates were similar between low-dose (50 IU FVIII kg(-1) three times a week) and high-dose (200 IU FVIII kg(-1) daily) regimens. However, patients receiving low-dose ITI took longer to achieve various ITI milestones and had a significantly higher bleed rate per month compared with the high-dose group (0.62 vs. 0.28; P = 0.00024), findings with important clinical implications. Inhibitor patients with poor prognostic features should be treated with a high-dose protocol. This conclusion is supported by a meta-analysis of the International Immune Tolerance Registry and North American Immune Tolerance Registry and by data from Germany showing good success rates with the high-dose, high-frequency Bonn protocol in poor prognosis patients. Type of concentrate also appears to have an influence on ITI success rates in this patient subgroup, with evidence suggesting an advantage for VWF-containing plasma-derived FVIII concentrates over recombinant or VWF-free concentrates. The ongoing prospective

  16. Long-term tolerability of capnography and respiratory inductance plethysmography for respiratory monitoring in pediatric patients treated with patient-controlled analgesia

    Science.gov (United States)

    Miller, Karen M.; Kim, Andrew Y.; Yaster, Myron; Kudchadkar, Sapna R.; White, Elizabeth; Fackler, James; Monitto, Constance L.

    2016-01-01

    Background The Anesthesia Patient Safety Foundation has advocated the use of continuous electronic monitoring of oxygenation and ventilation to preemptively identify opioid-induced respiratory depression. In adults, capnography is the gold standard in respiratory monitoring. An alternative technique used in sleep laboratories is respiratory inductance plethysmography (RIP). However, it is not known if either monitor is well tolerated by pediatric patients for prolonged periods of time. Aim The goal of this study was to determine whether capnography or RIP is better tolerated in non-intubated, spontaneously breathing pediatric patients being treated with intravenous patient-controlled analgesia (IVPCA). Methods Nasal cannula capnography with oral sampling and thoracic and abdominal inductance plethysmography bands were placed along with routine monitors on pediatric patients being treated for acute pain with IVPCA. Study monitors were left in place for as long as they were tolerated by the patient, for a maximum of 24 consecutive hours. If the patient did not wear a particular study monitor for any reason, but tolerated the remaining monitor, participation in the study continued. If the patient would not wear either monitor, participation was terminated. Results Twenty-six patients (18 female, 8 male, average age 10.1 ± 5.5 years) consented to participate, but only 14 patients attempted to wear one or both devices. Among those who wore either device, median time to device removal was 8.33 hours (range 0.3–23.6 hours) for capnography and 23.5 hours (range 0.7–24 hours) for RIP bands. Conclusion Children did not tolerate wearing capnography cannulae for prolonged periods of time, limiting the usefulness of this device as a continuous monitor of ventilation in children. RIP bands were better tolerated; however, they require further assessment of their utility. Until more effective, child-friendly monitors are developed and their utility validated, guidelines

  17. Autoantigens produced in plants for oral tolerance therapy of autoimmune diseases.

    Science.gov (United States)

    Ma, S; Jevnikar, A M

    1999-01-01

    Oral administration of protein antigens can induce antigen-specific immune hyporesponsiveness and may be useful in treating autoimmune diseases or preventing transplant rejection. However, the therapeutic value of oral tolerance may be limited when candidate autoantigens cannot be produced by conventional system in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can produce hugh quantities of functional mammalian proteins at extremely competitive cost. Furthermore, transgenic food plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Here we show that the diabetes-associated autoantigen glutamic acid decarboxylase (GAD) is efficiently expressed in both tobacco and potato plants, and that mice, when fed with fresh transgenic potato tubers, are fully protected from diabetes.

  18. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children.

    Science.gov (United States)

    Rosewich, M; Schulze, J; Eickmeier, O; Telles, T; Rose, M A; Schubert, R; Zielen, S

    2010-06-01

    Specific immunotherapy (SIT) is a well-established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10.2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL-adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgG(grass)) and IgG4(grass) by antibody blocking properties on basophil activation, and by induction of CD4(+), CD25(+) and forkhead box P3 (FoxP3(+)) regulatory T cells (T(reg)). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P adjuvant MPL needs at least two courses to establish tolerance.

  19. The "muffin test"--an alternative to the oral glucose tolerance test for detecting impaired glucose tolerance.

    Science.gov (United States)

    Traub, Michael L; Jain, Akas; Maslow, Bat-Sheva; Pal, Lubna; Stein, Daniel T; Santoro, Nanette; Freeman, Ruth

    2012-01-01

    The aim of this study was to compare the effectiveness of the "muffin test" (MT) with that of the oral glucose tolerance test (OGTT) in diagnosing impaired glucose tolerance (IGT). This is a cross-sectional study in a single academic institution. The participants were 73 women aged 42 to 58 years, less than 36 months after menopause, recruited for the Kronos Early Estrogen Prevention Study Trial. After a 10-hour fasting blood draw, the participants were provided a muffin and a beverage. Two-hour glucose levels were assessed. A subset underwent metabolic testing consisting of an OGTT (n = 12) and a mixed-meal tolerance test (n = 10). The main outcome measures were the prevalence of IGT and 2-hour glucose measurements after each testing method. Two-hour glucose levels were linearly related to fasting values by multivariable linear regression. This association was exaggerated in overweight (body mass index, 25 kg/m2) women (coefficient, 1.43; P 0.05); 2-hour glucose levels after OGTT were slightly lower than after the mixed-meal tolerance test (P < 0.05). The prevalence of IGT was 11% (8 of 73). Fasting plasma glucose alone would have missed 63% of cases (five of eight cases). The MT demonstrated 100% sensitivity and specificity for diagnosing IGT compared with the gold standard OGTT. This small pilot study should be confirmed in a larger prospective group of participants.

  20. Oral versus vaginal misoprostol for induction of labor in Enugu, Nigeria: a randomized controlled trial.

    Science.gov (United States)

    Ezechukwu, Paschalina Constance; Ugwu, Emmanuel Onyebuchi; Obi, Samuel Nnamdi; Chigbu, Chibuike Ogwuegbu

    2015-03-01

    The study aimed at comparing the effectiveness and maternal satisfaction of oral misoprostol with vaginal misoprostol for induction of labor at term. A randomized controlled trial of 140 term pregnant women at the University of Nigeria Teaching Hospital Enugu, Nigeria, was conducted from April 2011 to May 2012. The women were equally randomized into two groups (A and B) to receive oral and vaginal misoprostol, respectively. The vaginal route reduced the mean induction-vaginal delivery interval by four-and-half hours (20.7 ± 12.1 vs. 16.2 ± 10.4; mean difference: 4.50, 95% CI 0.63-0.82; p = 0.02). Furthermore, the mean dose of misoprostol required to achieve induction of labor and the mean duration of oxytocin augmentation when indicated were significantly less in the vaginal group than in the oral group (2.5 ± 1.3 vs. 2.0 ± 1.1; mean difference: 0.50, 95% CI 0.10-0.90; p = 0.02 and 4.6 ± 3.2 vs. 3.4 ± 3.1; mean difference: 1.20, 95% CI 0.15-0.23; p = 0.03 respectively). However, neonatal complications and maternal satisfaction were similar between the two groups. Both routes of administration are effective in the induction of labor at term and have comparable maternal satisfaction. However, the vaginal route has the added advantage of shorter induction-delivery interval among others, and thus should be highly considered when induction of labor is indicated at term.

  1. Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy.

    Science.gov (United States)

    Kim, Dong Wook; Gu, Nami; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Kim, Hwa Suk; Oh, Jeeyoung; Lee, Sang Kun

    2012-01-01

    The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  2. Immune tolerance induction using fetal directed placental injection in rodent models: a murine model.

    Directory of Open Access Journals (Sweden)

    Kei Takahashi

    Full Text Available Induction of the immune response is a major problem in replacement therapies for inherited protein deficiencies. Tolerance created in utero can facilitate postnatal treatment. In this study, we aimed to induce immune tolerance towards a foreign protein with early gestational cell transplantation into the chorionic villi under ultrasound guidance in the murine model.Pregnant C57BL/6 (B6 mice on day 10 of gestation were anesthetized and imaged by high resolution ultrasound. Murine embryos and their placenta were positioned to get a clear view in B-mode with power mode of the labyrinth, which is the equivalent of chorionic villi in the human. Bone marrow cells (BMCs from B6-Green Fluorescence Protein (B6GFP transgenic mice were injected into the fetal side of the placenta which includes the labyrinth with glass microcapillary pipettes. Each fetal mouse received 2 x 105 viable GFP-BMCs. After birth, we evaluated the humoral and cell-mediated immune response against GFP.Bone marrow transfer into fetal side of placenta efficiently distributed donor cells to the fetal mice. The survival rate of this procedure was 13.5%(5 out of 37. Successful engraftment of the B6-GFP donor skin grafts was observed in all recipient (5 out of 5 mice 6 weeks after birth. Induction of anti-GFP antibodies was completely inhibited. Cytotoxic immune reactivity of thymic cells against cells harboring GFP was suppressed by ELISPOT assay.In this study, we utilized early gestational placental injection targeting the murine fetus, to transfer donor cells carrying a foreign protein into the fetal circulation. This approach is sufficient to induce both humoral and cell-mediated immune tolerance against the foreign protein.

  3. Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice.

    Science.gov (United States)

    Steimle, Alex; Frick, Julia-Stefanie

    2016-01-01

    How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.

  4. Re-induction of desiccation tolerance after germination of Cedrela fissilis Vell. seeds.

    Science.gov (United States)

    Masetto, Tathiana E; Faria, Jose M; Fraiz, Ana C R

    2014-09-01

    This work aimed to characterize the re-induction of desiccation tolerance (DT) in germinated seeds, using polyethylene glycol (PEG 8000). Cell changes were investigated through cytological assays (cell viability and transmission electronic microscopy) as well as DNA integrity during loss and re-establishment of DT. The loss of DT was characterized by drying germinated seeds with different radicle lengths (1, 2, 3, 4 and 5 mm) in silica gel, decreasing the moisture content to ten percentage points intervals, followed by pre-humidification (100% RH / 24 h) and rehydration. To re-induce DT, germinated seeds were treated for 72 h with PEG (-2.04 MPa) and PEG (-2.04 MPa) + ABA (100 µM) before dehydration. Germinated seeds did not tolerate desiccation to 10% moisture content, irrespectively of the radicle length. However, when incubated in PEG, those with 1 and 2 mm long radicle attained 71% and 29% survival, respectively. The PEG+ABA treatment was efficient to re-establish DT in seeds with 1 mm long radicles (100% survival). The ultrastructural assays of the cells of germinated seeds with 2 and 5 mm length confirmed the obtained physiological results. Germinated seeds of C. fissilis constitute a useful tool for desiccation tolerance investigations.

  5. Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

    Science.gov (United States)

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2016-02-01

    The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels.

  6. Tolerability and pharmacokinetics of ebrotidine in healthy subjects given single and repeated oral doses.

    Science.gov (United States)

    Farré, M; Roset, P N; Badenas, J M; Ugena, B; Márquez, M; Albet, C; Herrero, E; Ortiz, J A

    1997-04-01

    The tolerability and safety of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) and its basic pharmacokinetic parameters were determined after its oral administration to healthy volunteers. Sixteen subjects were selected to participate in two different studies: an increasing single dose study to determine the maximal tolerated dose (from 25 to 1600 mg), and a multiple dose study (stepped doses from 400 to 1600 mg daily for 12 days). The results of the studies showed that ebrotidine has a good tolerability. Vital signs and laboratory tests were not influenced by the study treatment. No clinically relevant adverse effects were reported during the investigation. Ebrotidine reached peak plasma concentrations 2-3 h after oral administration. Its elimination half-life ranged from 9 to 14 h. In conclusion, ebrotidine was well tolerated after administration of oral single doses of up to 1600 mg, and after repeated administration of up to 800 mg/12 h for 12 days.

  7. Gastric Helicobacter Infection Inhibits Development of Oral Tolerance to Food Antigens in Mice

    Science.gov (United States)

    Matysiak-Budnik, Tamara; van Niel, Guillaume; Mégraud, Francis; Mayo, Kathryn; Bevilacqua, Claudia; Gaboriau-Routhiau, Valérie; Moreau, Marie-Christiane; Heyman, Martine

    2003-01-01

    The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-“tolerized” mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide. PMID:12933867

  8. Clinical pharmacokinetics and tolerability of dotarizine in healthy subjects after single and multiple oral administration.

    Science.gov (United States)

    Farré, M; Roset, P N; Llorente, M; Márquez, M; Albet, C; Pérez, J A; Herrero, E; Ortíz, J A

    1997-06-01

    Dotarizine is a new diphenylmethylpiperazine derivative with Ca2+ channel blocking properties and inhibitory effects on 5-HT2A and 5-HT2C receptors. Previous pilot studies in healthy volunteers demonstrated a good tolerability after single and multiple dosing. Dotarizine appeared to be rapidly and extensively metabolized to an active compound (FI-6020). We aimed to study the physiologic, subjective and psychomotor acute effects of oral dotarizine after single dose administration, to evaluate the tolerability and safety after multiple dosing over 2 weeks, and to study the pharmacokinetic parameters and linearity after single and multiple administration. Two different studies were carried out in 2 groups of 8 healthy male volunteers. Oral single doses of dotarizine 50, 100 and 200 mg were administered in a randomized, double-blind, crossover, placebo-controlled trial. Oral doses of 50 mg twice daily were administered in an open trial over 14 days. Drug effect assessments included vital signs, collection of adverse events, ECG and blood and urine safety evaluations, subjective effects, psychomotor performance tasks and blood sampling. Dotarizine and its metabolite were determined by gas chromatography with N-P detector. The results showed a good tolerability of dotarizine after single oral doses as well as multiple oral doses over 14 days. No clinically relevant adverse events were reported during the study. The highest single dose (200 mg) produced a slight increase in sedation-related symptoms as well as a slight impairment in psychomotor performance tasks. Dotarizine and its major metabolite proved linear kinetics at single doses. The administration of oral doses of dotarizine 50 mg b.i.d. reached the steady state after the 7th day of treatment. The pharmacokinetic parameters remained similar from day 7 to day 14. The terminal elimination half-life of dotarizine and its metabolite appeared to be between 7 and 12 h.

  9. DSP-Based Sensor Fault Detection and Post Fault-Tolerant Control of an Induction Motor-Based Electric Vehicle

    Directory of Open Access Journals (Sweden)

    Bekheïra Tabbache

    2012-01-01

    Full Text Available This paper deals with sensor fault detection within a reconfigurable direct torque control of an induction motor-based electric vehicle. The proposed strategy concerns current, voltage, and speed sensors faults that are detected and followed by post fault-tolerant control to allow the vehicle continuous operation. The proposed approach is validated through experiments on an induction motor drive and simulations on an electric vehicle using a European urban and extraurban driving cycle.

  10. Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance

    Directory of Open Access Journals (Sweden)

    Nina Pilat

    2015-01-01

    Full Text Available Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM transplantation (BMT model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+ in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 106 cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting.

  11. Myeloid derived suppressor cells and their role in tolerance induction in cancer.

    Science.gov (United States)

    Fujimura, Taku; Mahnke, Karsten; Enk, Alexander H

    2010-07-01

    Myeloid derived suppressor cells (MDSCs) comprise a phenotypically heterogeneous population of cells, which can be found in tumor-bearing mice and in patients with cancer. MDSCs play a central role in the induction of peripheral tolerance. Together with regulatory T cells (Tregs) they promote an immunosuppressive environment in tumor-bearing hosts. The phenotype of MDSCs differs in humans and mice, and the exact mechanisms of their suppressive function are still controversially discussed. In summary, MDSCs are a group of phenotypically heterogeneous cells of myeloid origin that have common biological activities. In this review, we discuss the definition of MDSCs, the proposed mechanisms of expansion and the recruitment and activation of MDSCs, as well as their biological activities in tumorbearing hosts to assess the potential therapeutic applications.

  12. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial

    DEFF Research Database (Denmark)

    de Groot, Kirsten; Harper, Lorraine; Jayne, David R W

    2009-01-01

    BACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were compu...

  13. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis : long-term follow-up

    NARCIS (Netherlands)

    Harper, Lorraine; Morgan, Matthew D.; Walsh, Michael; Hoglund, Peter; Westman, Kerstin; Flossmann, Oliver; Tesar, Vladimir; Vanhille, Phillipe; de Groot, Kirsten; Luqmani, Raashid; Felipe Flores-Suarez, Luis; Watts, Richard; Pusey, Charles; Bruchfeld, Annette; Rasmussen, Niels; Blockmans, Daniel; Savage, Caroline O.; Jayne, David

    2012-01-01

    Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were

  14. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Pedersen, Susanne Brix; Frøkiær, Hanne

    2004-01-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mice...... of the first (F1) and second (F2) offspring generation bred on a soya protein-free diet were used either directly or were transferred between the soya-containing and soya protein-free diet during pregnancy or neonatal life. The mice were compared as to levels of naturally occurring specific antibodies analysed...... by ELISA, and to the presence of oral tolerance detected as a suppressed antibody and cell-proliferation response upon immunisation with soya protein. F0 mice generated soya-specific antibodies, while oral tolerance to the same soya proteins was also clearly induced. When F0 dams were transferred to soya...

  15. Toll-Like Receptor 2 as a Regulator of Oral Tolerance in the Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Matthew C. Tunis

    2014-01-01

    Full Text Available Food allergy, other adverse immune responses to foods, inflammatory bowel disease, and eosinophilic esophagitis have become increasingly common in the last 30 years. It has been proposed in the “hygiene hypothesis” that dysregulated immune responses to environmental microbial stimuli may modify the balance between tolerance and sensitization in some patients. Of the pattern recognition receptors that respond to microbial signals, toll-like receptors (TLRs represent the most investigated group. The relationship between allergy and TLR activation is currently at the frontier of immunology research. Although TLR2 is abundant in the mucosal environment, little is known about the complex relationship between bystander TLR2 activation by the commensal microflora and the processing of oral antigens. This review focuses on recent advances in our understanding of the relationship between TLR2 and oral tolerance, with an emphasis on regulatory T cells, eosinophils, B cells, IgA, intestinal regulation, and commensal microbes.

  16. Value of oral glucose tolerance test in the acute phase of myocardial infarction

    OpenAIRE

    Grabczewska Zofia; Bronisz Marek; Kubica Aldona; Sukiennik Adam; Swiatkiewicz Iwona; Gierach Joanna; Fabiszak Tomasz; Magielski Przemyslaw; Kozinski Marek; Bronisz Agata; Sinkiewicz Anna; Junik Roman; Kubica Jacek

    2011-01-01

    Abstract Background Although European guidelines advise oral glucose tolerance test (OGTT) in patients with acute myocardial infarction (AMI) before or shortly after hospital discharge, data supporting this recommendation are inconclusive. We aimed to analyze whether disturbances in glucose metabolism diagnosed before hospital discharge in AMI patients represents a latent pre-existing condition or rather temporary finding. Additionally, we planned to investigate the value of pre-selected glyc...

  17. Hemoglobin A1c Versus Oral Glucose Tolerance Test in Postpartum Diabetes Screening

    OpenAIRE

    Picón, María José; Murri, Mora; Muñoz, Araceli; Fernández-García, José Carlos; Gomez-Huelgas, Ricardo; Francisco J Tinahones

    2012-01-01

    OBJECTIVE To determine the usefulness of measuring hemoglobin A1c (A1C), alone or combined with the fasting glucose test, compared with the oral glucose tolerance test (OGTT) for the reassessment of the carbohydrate metabolism status in postpartum women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We evaluated the status of carbohydrate metabolism by performing the OGTT and fasting glucose and A1C tests in 231 postpartum women with prior GDM 1 year after ...

  18. Tolerability of oral xylitol solution in young children: implications for otitis media prophylaxis.

    Science.gov (United States)

    Vernacchio, Louis; Vezina, Richard M; Mitchell, Allen A

    2007-01-01

    Xylitol, given as 2g orally five times-a-day, significantly reduces the incidence of acute otitis media (AOM) in children. A less frequent dosing schedule, if tolerable and efficacious, would promote the more widespread use of this treatment. We sought to determine the tolerability and acceptability in young children of oral xylitol solution at doses of 5g three times-a-day (TID) and 7.5g once daily (QD). The study was a 3-month randomized placebo-controlled trial of the tolerability and acceptability of oral xylitol solution in 120 children 6-36 months of age performed in the SCOR Network. Study withdrawals and unscheduled medical visits for gastrointestinal complaints did not differ significantly among the study groups. The proportions of subjects in the xylitol TID group who experienced excessive gas or diarrhea at months 1, 2, and 3 were 22.7%, 10.0%, and 14.3%, respectively, and in the xylitol QD group were 27.3%, 17.4%, and 14.3%, respectively, and these did not differ from the placebo groups. The proportions who accepted the study solution easily or with only minor difficulty at 1, 2, and 3 months in the xylitol TID group were 77.3%, 90.0%, and 90.5% and in the xylitol QD group, 77.3%, 82.6%, and 90.5%, respectively. Oral xylitol solution at dosages of 5g TID and 7.5g QD is well-tolerated by young children. Given the potential for xylitol as a safe, inexpensive option for AOM prophylaxis, clinical trials using these dosages of xylitol can be conducted.

  19. Coil Design for High Misalignment Tolerant Inductive Power Transfer System for EV Charging

    Directory of Open Access Journals (Sweden)

    Kafeel Ahmed Kalwar

    2016-11-01

    Full Text Available The inductive power transfer (IPT system for electric vehicle (EV charging has acquired more research interest in its different facets. However, the misalignment tolerance between the charging coil (installed in the ground and pick-up coil (mounted on the car chassis, has been a challenge and fundamental interest in the future market of EVs. This paper proposes a new coil design QDQ (Quad D Quadrature that maintains the high coupling coefficient and efficient power transfer during reasonable misalignment. The QDQ design makes the use of four adjacent circular coils and one square coil, for both charging and pick-up side, to capture the maximum flux at any position. The coil design has been modeled in JMAG software for calculation of inductive parameters using the finite element method (FEM, and its hardware has been tested experimentally at various misaligned positions. The QDQ coils are shown to be capable of achieving good coupling coefficient and high efficiency of the system until the misalignment displacement reaches 50% of the employed coil size.

  20. Development of gene transfer for induction of antigen-specific tolerance

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    Brandon K Sack

    2014-01-01

    Full Text Available Gene replacement therapies, like organ and cell transplantation, are likely to introduce neoantigens that elicit rejection via humoral and/or effector T-cell immune responses. Nonetheless, thanks to an ever-growing body of preclinical studies; it is now well accepted that gene transfer protocols can be specifically designed and optimized for induction of antigen-specific immune tolerance. One approach is to specifically express a gene in a tissue with a tolerogenic microenvironment such as the liver or thymus. Another strategy is to transfer a particular gene into hematopoietic stem cells or immunological precursor cells thus educating the immune system to recognize the therapeutic protein as “self.” In addition, expression of the therapeutic protein in protolerogenic antigen-presenting cells such as immature dendritic cells and B cells has proven to be promising. All three approaches have successfully prevented unwanted immune responses in preclinical studies aimed at the treatment of inherited protein deficiencies, e.g., lysosomal storage disorders and hemophilia, and of type 1 diabetes and multiple sclerosis. In this review, we focus on current gene transfer protocols that induce tolerance, including gene delivery vehicles and target tissues, and discuss successes and obstacles in different disease models.

  1. Acid stress response and protein induction in Campylobacter jejuni isolates with different acid tolerance

    DEFF Research Database (Denmark)

    Birk, Tina; Wik, Monica Takamiya; Lametsch, René

    2012-01-01

    BACKGROUND: During the transmission route from poultry to the human host, the major foodborne pathogen C. jejuni may experience many types of stresses, including low pH caused by different acids. However, not all strains are equally sensitive to the stresses. The aim of this study was to investig......BACKGROUND: During the transmission route from poultry to the human host, the major foodborne pathogen C. jejuni may experience many types of stresses, including low pH caused by different acids. However, not all strains are equally sensitive to the stresses. The aim of this study...... was to investigate the response to acid stress of three sequenced C. jejuni strains with different acid tolerances using HCl and acetic acid. RESULTS: Two-dimensional gel electrophoresis was used for proteomic analysis and proteins were radioactively labelled with methionine to identify proteins only related to acid...... with MALDI-TOF-TOF. The most acid-sensitive isolate was C. jejuni 327, followed by NCTC 11168 and isolate 305 as the most tolerant. Overall, induction of five proteins was observed within the pI range investigated: 19 kDa periplasmic protein (p19), thioredoxin-disulfide (TrxB), a hypothetical protein Cj0706...

  2. Hyperlipidemia Alters Regulatory T Cell Function and Promotes Resistance to Tolerance Induction Through Costimulatory Molecule Blockade.

    Science.gov (United States)

    Bagley, J; Yuan, J; Chandrakar, A; Iacomini, J

    2015-09-01

    Recent work from our laboratory has shown that hyperlipidemia promotes accelerated rejection of vascularized cardiac allografts in mice by inducing anti-donor Th17 reactivity and production of IL-17. Here, we show that hyperlipidemia also affects FoxP3(+) regulatory T cells (Tregs). Hyperlipidemia promotes the development of Tregs that express low levels of CD25. Hyperlipidemia also promotes a decrease in central Tregs and an increase in effector Tregs that appears to account for the increase in the frequency of CD25(low) Tregs. Alterations in Treg subsets also appear to lead to alterations in Treg function. The ability of FoxP3(+) , CD25(high) , CD4(+) Tregs from hyperlipidemic mice to inhibit proliferation of effector T cells stimulated with anti-CD3 and CD28 was reduced when compared with Tregs from control mice. Regulatory T cells isolated from hyperlipidemic recipients exhibit increased activation of Akt, and a reduction in Bim levels that permits the expansion of FoxP3(+) CD25(low) CD4(+) T cells. Hyperlipidemic mice were also resistant to tolerance induction using costimulatory molecule blockade consisting of anti-CD154 and CTLA4Ig, a strategy that requires Tregs. Together, our data suggest that hyperlipidemia profoundly affects Treg subsets and function as well as the ability to induce tolerance.

  3. CROSS-TOLERANCE MECHANISM INDUCTION IN MELON SEEDS BY PRIMING PRIOR DRYING

    Directory of Open Access Journals (Sweden)

    Jean Marcel Sousa Lira

    2015-04-01

    Full Text Available The loss of benefits after re-drying is one of the drawbacks of the seed priming technique. Different types of stresses have been used before re-drying to preserve the priming benefits. This process may be seen as promoting cross tolerance to increase the defense mechanisms that prevent loss of viability in seeds primed after drying. We tested the effect of some stresses to induce cross-tolerance and different drying conditions with the aim of maintaining priming benefits in melon seeds. The seeds were primed in an aerated KNO3 solution (0.35M, -1.7MPa, 25 °C, in the dark for six days. The primed seeds were then submitted to slow drying, fast drying, cold shock + slow drying, cold shock + fast drying, heat shock + slow drying, heat shock + fast drying, PEG + slow drying, PEG + fast drying, ABA + slow drying, ABA + fast drying and no drying (planted directly after priming. We evaluated antioxidant enzyme activities (SOD, CAT and APX, germinability, mean time of germination (MTG and mean rate of germination (MRG. A completely randomized design was used with three repetitions of 50 seeds in each treatment. Data were analyzed by ANOVA and means were compared by the Scott-Knott test (p ≤ 0.05. ABA increased SOD activity after drying and CAT activity was reduced by priming. APX activity was not observed. The stress submission prior to re-drying improved the MRG and reduced MTG. Therefore, the induction of the cross-tolerance mechanism could be effective to maintain priming benefits in melon seeds.

  4. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China); Li, Wen-Bao, E-mail: wbli92128@yahoo.com [Sanlugen PharmaTech, Rm 506, No. 2766 Yingxiu Road, Jinan 250101 (China); Qu, Xian-Jun, E-mail: qxj@sdu.edu.cn [Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012 (China)

    2013-08-23

    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.

  5. Fault-tolerant control for current sensors of doubly fed induction generators based on an improved fault detection method

    DEFF Research Database (Denmark)

    Li, Hui; Yang, Chao; Hu, Yaogang

    2014-01-01

    Fault-tolerant control of current sensors is studied in this paper to improve the reliability of a doubly fed induction generator (DFIG). A fault-tolerant control system of current sensors is presented for the DFIG, which consists of a new current observer and an improved current sensor fault...... detection algorithm, and fault-tolerant control system are investigated by simulation. The results indicate that the outputs of the observer and the sensor are highly coherent. The fault detection algorithm can efficiently detect both soft and hard faults in current sensors, and the fault-tolerant control...... system can effectively tolerate both types of faults. © 2013 Published by Elsevier Ltd. All rights reserved....

  6. Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Andreas Daiber

    2012-01-01

    Full Text Available Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1 could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN, a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.

  7. Labour Induction With Randomized Comparison Of Oral And Intravaginal Misoprostol In Post Date Multigravida Women

    Science.gov (United States)

    Ayaz, Aqueela; Saeed, Shazia; Farooq, Mian Usman; Ahmad, Iftikhar; Ali Bahoo, Muhammad Luqman; Saeed, Muhammad

    2009-01-01

    The efficacy and safety of oral versus vaginal misoprostol for elective induction of labor in post date multigravida with an unfavourable cervix was compared over a period of one year in the Bahawal Victoria Hospital, Bahawalpur, Pakistan. Eightyeight multigravida post date women were divided into two groups and given 50 mg misoprostol orally and 50 mg intravaginally, respectively. The induction to onset of significant uterine contractions and delivery intervals were lower in the first group (7.8 h vs. 8.9 h) when compared to (10.4 h vs. 12 h). The first group had a higher rate of Caesarean section (7% vs. 4%; p>0.05), uterine hyperstimulation (9% vs. 5%; p>0.05), uterine tachysystole (23% vs. 14%; p>0.05) and neonatal admissions to intensive care unit (12% vs. 4%; p>0.05) when compared to second group. Fifty mg oral misoprostol has the potential to induce labor as safely and effectively as the intravaginal route. PMID:22589646

  8. Induction of tolerance to cardiac allografts using donor splenocytes engineered to display on their surface an exogenous fas ligand protein.

    Science.gov (United States)

    Yolcu, Esma S; Gu, Xiao; Lacelle, Chantale; Zhao, Hong; Bandura-Morgan, Laura; Askenasy, Nadir; Shirwan, Haval

    2008-07-15

    The critical role played by Fas ligand (FasL) in immune homeostasis renders this molecule an attractive target for immunomodulation to achieve tolerance to auto- and transplantation Ags. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging. Therefore, we tested the efficacy of donor splenocytes rapidly and efficiently engineered to display on their surface a chimeric form of FasL protein (SA-FasL) for tolerance induction to cardiac allografts. The i.p. injection of ACI rats with Wistar-Furth rat splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third-party cardiac allografts. Tolerance was associated with apoptosis of donor reactive T effector cells and induction/expansion of CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells. Treg cells played a critical role in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naive unmanipulated ACI rats resulted in indefinite survival of secondary Wistar-Furth grafts. Immunomodulation with allogeneic cells rapidly and efficiently engineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapy with potential application to regenerative medicine, transplantation, and autoimmunity.

  9. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults.

    Science.gov (United States)

    Moore, M C; Cherrington, A D; Mann, S L; Davis, S N

    2000-12-01

    In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

  10. A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

    Science.gov (United States)

    Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

    2015-01-01

    Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures.

  11. Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

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    Raul Ramos Furtado Dias

    Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

  12. Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

    Science.gov (United States)

    Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

    2014-01-01

    Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

  13. A20 is critical for the induction of Pam3CSK4-tolerance in monocytic THP-1 cells.

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    Jinyue Hu

    Full Text Available A20 functions to terminate Toll-like receptor (TLR-induced immune response, and play important roles in the induction of lipopolysacchride (LPS-tolerance. However, the molecular mechanism for Pam3CSK4-tolerance is uncertain. Here we report that TLR1/2 ligand Pam3CSK4 induced tolerance in monocytic THP-1 cells. The pre-treatment of THP-1 cells with Pam3CSK4 down-regulated the induction of pro-inflammatory cytokines induced by Pam3CSK4 re-stimulation. Pam3CSK4 pre-treatment also down-regulated the signaling transduction of JNK, p38 and NF-κB induced by Pam3CSK4 re-stimulation. The activation of TLR1/2 induced a rapid and robust up-regulation of A20, suggesting that A20 may contribute to the induction of Pam3CSK4-tolerance. This hypothesis was proved by the observation that the over-expression of A20 by gene transfer down-regulated Pam3CSK4-induced inflammatory responses, and the down-regulation of A20 by RNA interference inhibited the induction of tolerance. Moreover, LPS induced a significant up-regulation of A20, which contributed to the induction of cross-tolerance between LPS and Pam3CSK4. A20 was also induced by the treatment of THP-1 cells with TNF-α and IL-1β. The pre-treatment with TNF-α and IL-1β partly down-regulated Pam3CSK4-induced activation of MAPKs. Furthermore, pharmacologic inhibition of GSK3 signaling down-regulated Pam3CSK4-induced A20 expression, up-regulated Pam3CSK4-induced inflammatory responses, and partly reversed Pam3CSK4 pre-treatment-induced tolerance, suggesting that GSK3 is involved in TLR1/2-induced tolerance by up-regulation of A20 expression. Taken together, these results indicated that A20 is a critical regulator for TLR1/2-induced pro-inflammatory responses.

  14. Acid stress response and protein induction in Campylobacter jejuni isolates with different acid tolerance

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    Birk Tina

    2012-08-01

    Full Text Available Abstract Background During the transmission route from poultry to the human host, the major foodborne pathogen C. jejuni may experience many types of stresses, including low pH caused by different acids. However, not all strains are equally sensitive to the stresses. The aim of this study was to investigate the response to acid stress of three sequenced C. jejuni strains with different acid tolerances using HCl and acetic acid. Results Two-dimensional gel electrophoresis was used for proteomic analysis and proteins were radioactively labelled with methionine to identify proteins only related to acid exposure. To allow added radioactive methionine to be incorporated into induced proteins, a modified chemically defined broth was developed with the minimal amount of methionine necessary for satisfactory growth of all strains. Protein spots were analyzed using image software and identification was done with MALDI-TOF-TOF. The most acid-sensitive isolate was C. jejuni 327, followed by NCTC 11168 and isolate 305 as the most tolerant. Overall, induction of five proteins was observed within the pI range investigated: 19 kDa periplasmic protein (p19, thioredoxin-disulfide (TrxB, a hypothetical protein Cj0706 (Cj0706, molybdenum cofactor biosynthesis protein (MogA, and bacterioferritin (Dps. Strain and acid type dependent differences in the level of response were observed. For strain NCTC 11168, the induced proteins and the regulator fur were analysed at the transcriptomic level using qRT-PCR. In this transcriptomic analysis, only up-regulation of trxB and p19 was observed. Conclusions A defined medium that supports the growth of a range of Campylobacter strains and suitable for proteomic analysis was developed. Mainly proteins normally involved in iron control and oxidative stress defence were induced during acid stress of C. jejuni. Both strain and acid type affected sensitivity and response.

  15. Tolerability assessment of a lectin fraction from Tepary bean seeds (Phaseolus acutifolius orally administered to rats

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    Roberto Ferriz-Martínez

    2015-01-01

    Full Text Available Our previous studies have shown that a lectin rich fraction (TBLF extracted from Tepary bean seeds differentially inhibits cancer cells proliferation in vitro. Before testing the in vivo anticancer effect, the acute and subchronic toxicological assays in rats were conducted, where an oral dose of 50 mg/body weight kg was determined as the NOAEL. This study evaluated the resistance to digestion and complete blood count (CBC after 24 h of the orally administered 50 mg/kg TBLF. The digestion resistance test showed lectins activity retention after 72 h and the CBC study showed a high level of eosinophils, suggesting an allergic-like response. Tolerability was assayed after 6 weeks of treatment by dosing with an intragastric cannula every third day per week. It was observed a transient reduction in food intake and body weight in the first weeks, resulting in body weight gain reduction of 10% respect to the control group at the end of the study. Additionally, organs weight, histopathological analysis and blood markers for nutritional status and for liver, pancreas and renal function were not affected. Our results suggest that 50 mg/kg TBLF administered by oral route, exhibit no toxicity in rats and it was well tolerated. Further studies will focus on long-term studies.

  16. Zonula occludens toxin (Zot) interferes with the induction of nasal tolerance to gliadin.

    Science.gov (United States)

    Rossi, Mauro; Maurano, Francesco; Luongo, Diomira; Fasano, Alessio; Uzzau, Sergio; Auricchio, Salvatore; Troncone, Riccardo

    2002-05-01

    Both nasal and oral administration of soluble protein antigens (Ags) induce tolerance, a phenomenon that has hampered mucosal vaccine design. To produce active immunity the use of adjuvants co-administered with soluble Ags is required. Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) were found to be powerful mucosal adjuvants, but they are not suitable for clinical use because of their associated toxicity. Therefore, there is the need to develop alternative strategies to deliver Ag in order to induce immunoprotection. Among these innovative tools, a new toxin, Zonula occludens toxin (Zot), produced by phages in toxigenic strains of Vibrio cholerae, has been recently exploited for its adjuvant activity at the mucosal level. The present study was undertaken to further highlight the adjuvant properties of Zot. The ability of Zot to induce a mucosal response to gliadin was demonstrated per serum antibody production. In our established model of systemic tolerance to gliadin, induced by its nasal administration, we found a reduced production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) upon administration of gliadin alone. This immune suppression was reverted in mice receiving gliadin together with Zot. As previously shown, the down-regulation of Th1-like cytokines was found to be associated to a suppression of the T-cell proliferation, while such a suppression was completely reverted by Zot co-administration. In conclusion, these data confirm Zot as a good mucosal adjuvant, considering its ability to interfere with the suppression of specific cell mediated immunity, probably as a result of the increased dose and/or altered processing of Ag at mucosal level.

  17. Role of Cellular Immunity in Cow’s Milk Allergy: Pathogenesis, Tolerance Induction, and Beyond

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    Juandy Jo

    2014-01-01

    Full Text Available Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow’s milk proteins. Due to its very early introduction, cow’s milk allergy is one of the earliest and most common food allergies. For this reason cow’s milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow’s milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow’s milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization, development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow’s milk proteins. In addition, a possible interaction between immune mechanisms underlying cow’s milk allergy and other types of inflammation (infections and noncommunicable diseases is discussed.

  18. Induction of type XVI collagen expression facilitates proliferation of oral cancer cells.

    Science.gov (United States)

    Ratzinger, Sabine; Grässel, Susanne; Dowejko, Albert; Reichert, Torsten E; Bauer, Richard J

    2011-03-01

    Type XVI collagen belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). Recently, high affinity to integrin alpha1beta1 has been shown allowing cells expressing those integrins to attach and spread on recombinant type XVI collagen. Here, we show that type XVI collagen is overexpressed in dysplastic areas of mucosal epithelium from oral squamous cell carcinoma (OSCC) patients. Induction of its expression in OSCC cell lines (COLXVI cells) leads to an increased expression of Kindlin-1. Moreover, we demonstrate a significantly increased Kindlin-1/beta1-integrin interaction. Additionally, we detected a higher number of activated beta1-integrins in COLXVI cells and found a neo-expression of alpha1 integrin subunit on these cells. FACS analysis revealed a significantly higher amount of COLXVI cells in S-phase and G2/M-phase 6h after synchronisation leading to a markedly higher proliferation activity. Blocking beta1-integrins with a specific antibody resulted in reduced proliferation of COLXVI cells. In summary, we demonstrate that overexpression of type XVI collagen in aberrant oral keratinocytes leads to Kindlin-1 induction, increased Kindlin-1/beta1-integrin interaction, integrin activation and subsequently to a proliferative cellular phenotype.

  19. Estrogens, lactation and oral glucose tolerance test in the early puerperium.

    Science.gov (United States)

    Job, D; Eschwege, E

    1976-01-01

    An oral glucose tolerance test (OGTT) was performed on 98 women free from any known risk factor of diabetes on the fifth day of the puerperium. Results show that OGTT is greatly influenced by the conditions of lactation. A high proportion of abnormal curves (50%) is found among the group of women receiving estrogens as lactation suppressors at the time of the test. However, in breast feeding women or in non breast feeding women not given estrogen, the proportion of abnormal curves is less than 10%. It is concluded that the unexplained previously reported lack of specificity of the OGTT in the early puerperium could be related to hormonal treatment for lactation suppression.

  20. Gene array analysis of a rat model of liver transplant tolerance identifies increased complement C3 and the STAT-1/IRF-1 pathway during tolerance induction.

    Science.gov (United States)

    Cordoba, Shaun P; Wang, Chuanmin; Williams, Rohan; Li, Jian; Smit, Lynn; Sharland, Alexandra; Allen, Richard; McCaughan, Geoffrey; Bishop, Alex

    2006-04-01

    This study aimed to define the molecular mechanism during induction of spontaneous liver transplant tolerance using microarrays and to focus on molecular pathways associated with tolerance by meta-analysis with published studies. The differences in the early immune response between PVG to DA liver transplant recipients that are spontaneously tolerant (TOL) and PVG to Lewis liver transplants that reject (REJ) were examined. Spleens from TOL and REJ on days 1 and 3 were compared by 2 color microarray. Forty-six of 199 genes differentially expressed between TOL and REJ had an immunological function. More immune genes were increased in TOL vs. REJ on day 1, including STAT-1, IRF-1 and complement C3. Differential expression of selected genes was confirmed by quantitative RT-PCR. The results were compared to two published high-throughput studies of rat liver transplant tolerance and showed that C3 was increased in all three models, while STAT-1 and IRF-1 were increased in two models. The early increases in immune genes in TOL confirmed previous reports of an active early immune response in TOL. In conclusion, the increase in STAT-1, IRF-1 and complement component C3 in several models of liver transplant tolerance suggests that the STAT-1/IRF-1 apoptotic pathway and C3 may be involved in the tolerogenic mechanism.

  1. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance.

    Science.gov (United States)

    Chuprin, Anna; Avin, Ayelet; Goldfarb, Yael; Herzig, Yonatan; Levi, Ben; Jacob, Adi; Sela, Asaf; Katz, Shir; Grossman, Moran; Guyon, Clotilde; Rathaus, Moran; Cohen, Haim Y; Sagi, Irit; Giraud, Matthieu; McBurney, Michael W; Husebye, Eystein S; Abramson, Jakub

    2015-07-01

    Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire(+) mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.

  2. Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

    Science.gov (United States)

    Sun, Da-Li; Li, Wei-Ming; Li, Shu-Min; Cen, Yun-Yun; Xu, Qing-Wen; Li, Yi-Jun; Sun, Yan-Bo; Qi, Yu-Xing; Lin, Yue-Ying; Yang, Ting; Lu, Qi-Ping; Xu, Peng-Yuan

    2017-02-10

    Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P multi-modal early oral nutrition group (P multi-modal early oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery. Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014.

  3. Bowel Sounds Are Not Associated With Flatus, Bowel Movement, or Tolerance of Oral Intake in Patients After Major Abdominal Surgery.

    Science.gov (United States)

    Read, Thomas E; Brozovich, Marc; Andujar, Jose E; Ricciardi, Rocco; Caushaj, Philip F

    2017-06-01

    Auscultation for bowel sounds has been advocated by some clinicians as a method to determine the resolution of postoperative ileus. Our primary aim was to prospectively evaluate the relationships between bowel sounds and the ability to tolerate oral intake in patients after major abdominal surgery. Secondarily we aimed to evaluate relationships among bowel sounds, flatus and bowel movement, and oral intake. This was a prospective, blinded observational study. The study was conducted at Western Pennsylvania Hospital. A total of 124 adult patients undergoing major abdominal surgery were included. Data were collected by medical students blinded to the purpose of the study for 10 days postoperatively or until discharge, including the presence of bowel sounds (auscultation for 1 minute), flatus, bowel movement, and tolerance of oral intake (defined as ingestion of ≥1000 mL/24 h and each subsequent day without vomiting). Associations between paired variables were determined using ϕ coefficient testing. The study population consisted of 51 men and 73 women, with a mean age of 64 years (range, 20-92 y). The majority of patients (78/124 (63%)) underwent colorectal resection. The median length of hospital was 6 days. Bowel sounds were not associated with flatus, bowel movement, or tolerance of oral intake throughout the study period. The positive predictive value of bowel sounds in predicting flatus and bowel movement was low in the early postoperative period and remained Flatus correlated with bowel movement in the first 6 days postoperation, but neither flatus nor bowel movement was associated with tolerance of oral intake. The rate of tolerance of oral intake was relatively modest throughout the study period. Bowel sounds are not associated with flatus, bowel movement, or tolerance of oral intake after major abdominal surgery.

  4. [Usefulness of peristalsis, flatulence and evacuation for predicting oral route tolerance in patients subjected to major abdominal surgery].

    Science.gov (United States)

    Hernández-Hernández, Betsabé; Figueroa-Gallaga, Luis; Sánchez-Castrillo, Christian; Belmonte-Montes, Carlos

    2007-01-01

    to evaluate the usefulness of bowel sounds, flatus and bowel movement presence to predict tolerance of oral intake in patients following major abdominal surgery. nutrition is one of the most important factors in the management of postoperative care. The early oral intake has shown to contribute to a faster recovery. Traditionally the beginning of postoperative feeding after major abdominal surgery is delayed until bowel sounds, flatus and/or bowel movement are present although there is no enough medical evidence for their usefulness. We studied 88 patients following major abdominal surgery. We registered the presence of bowel sounds, flatus and bowel movement each 24 hours in the postoperative period. We analized the relationship between the presence of these signs and the ability to tolerate oral intake. Predictive values, sensitivity, specificity and ROC curves were calculated. results shown that bowel sounds have an acCeptable sensibility but a very low specificity to predict the ability to tolerate oral intake. Unlike bowel sounds, bowel movements shown a low sensibility and a high specificity. Flatus turned out to have and intermediate sensitivity and specificity in the prediction of tolerance of oral feeding. in this study any of these signs were shown as a reliable indicator for beginning oral feeding because they have a moderate to low usefulness.

  5. Ahmedabad tolerance induction protocol and chronic renal allograft dysfunction: pathologic observations and clinical implications

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    Trivedi Hargovind L

    2009-01-01

    Full Text Available Abstract Background Chronic Renal Allograft Dysfunction (CRAD is responsible for a large number of graft failures. We have abrogated acute T-cell rejections using Ahmedabad Tolerance Induction Protocol (ATIP with hematopoietic stem cell transplantation (HSCT under non-myeloablative conditioning pre-transplant. However B-cell mediated rejections and CRAD continue to haunt us. We carried out retrospective analysis of renal allograft biopsies performed in the last 4 years to evaluate the effect of ATIP on CRAD. Materials and methods Biopsies diagnosed as per modified Banff criteria belonged to 2 groups: ATIP under low dose immunosuppression of cyclosporine/Azathioprine/Mycofenolate mofetil+ Prednisolone, subjected to donor leucocyte transfusion, anti-T/B cell antibodies, low dose target specific irradiation, cyclophosphamide, cyclosporin followed by HSCT pre-transplant; controls who opted out of ATIP were transplanted under standard triple drug immunosuppression. Demographics of both groups were comparable. Results Incidence of chronic changes was higher in controls (17.5% vs. 10.98% in ATIP over a mean follow up of 151.9 months in the former and 130.9 months in the latter. Proteinuria and hypertension were higher in controls (48.4% vs. ATIP (32.7% with chronic transplant glomerulopathy, focal global sclerosis in 67.7% in controls vs. 46.7% in ATIP, acute on chronic T/B cell rejection in 51.6% controls vs. 28.1% ATIP, with peritubular capillary C4d deposits in 19.4% controls vs. 1.9% ATIP biopsies. Acute on chronic calcineurin inhibitor toxicity was higher in ATIP (71.9% vs. 48.4% in controls. Conclusion Chronic immune injury was less with ATIP vs controls as compared to a higher incidence of chronic calcineurin inhibitor toxicity in the former.

  6. Prevalence of diabetes in Catalonia (Spain): an oral glucose tolerance test-based population study.

    Science.gov (United States)

    Castell, C; Tresserras, R; Serra, J; Goday, A; Lloveras, G; Salleras, L

    1999-01-01

    The goal of this study was to investigate the prevalence of diabetes mellitus and impaired glucose tolerance in the adult population of Catalonia and study their association with obesity, central obesity, hypertension and smoking habit. A random sample of 3839 subjects aged 30-89 years participated in this cross-sectional study: 2214 subjects underwent a health examination with oral glucose tolerance test (OGTT) and 1625 were interviewed by phone. Diabetes prevalence (known and unknown) in the 30-89-year-old population was 10.3%, (95% CI: 9.1-11.6). In this age group, the prevalence rates of known diabetes, unknown diabetes and impaired glucose tolerance were 6.4, 3.9 and 11.9% in men and 6.9, 3.4 and 11.9% in women. The age adjusted prevalence to the world population for the 30-64-year-old age group was 6.1% (7.1% in men and 5.2% in women).The factors significantly associated with diabetes were age, obesity, hypertension and family history of diabetes. The high ratio of previously known diabetic cases to newly discovered ones, specially in the oldest age group, suggests good levels of awareness and medical services. The prevalence in Catalonia is similar to that observed in other Mediterranean countries.

  7. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice

    DEFF Research Database (Denmark)

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-01-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice...... in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine...... regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice....

  8. Oral perceptions of fat and taste stimuli are modulated by affect and mood induction.

    Directory of Open Access Journals (Sweden)

    Petra Platte

    Full Text Available This study examined the impact of three clinical psychological variables (non-pathological levels of depression and anxiety, as well as experimentally manipulated mood on fat and taste perception in healthy subjects. After a baseline orosensory evaluation, 'sad', 'happy' and 'neutral' video clips were presented to induce corresponding moods in eighty participants. Following mood manipulation, subjects rated five different oral stimuli, appearing sweet, umami, sour, bitter, fatty, which were delivered at five different concentrations each. Depression levels were assessed with Beck's Depression Inventory (BDI and anxiety levels were assessed via the Spielberger's STAI-trait and state questionnaire. Overall, subjects were able to track the concentrations of the stimuli correctly, yet depression level affected taste ratings. First, depression scores were positively correlated with sucrose ratings. Second, subjects with depression scores above the sample median rated sucrose and quinine as more intense after mood induction (positive, negative and neutral. Third and most important, the group with enhanced depression scores did not rate low and high fat stimuli differently after positive or negative mood induction, whereas, during baseline or during the non-emotional neutral condition they rated the fat intensity as increasing with concentration. Consistent with others' prior observations we also found that sweet and bitter stimuli at baseline were rated as more intense by participants with higher anxiety scores and that after positive and negative mood induction, citric acid was rated as stronger tasting compared to baseline. The observation that subjects with mild subclinical depression rated low and high fat stimuli similarly when in positive or negative mood is novel and likely has potential implications for unhealthy eating patterns. This deficit may foster unconscious eating of fatty foods in sub-clinical mildly depressed populations.

  9. Induction of Siglec-1 by Endotoxin Tolerance Suppresses the Innate Immune Response by Promoting TGF-β1 Production.

    Science.gov (United States)

    Wu, Yin; Lan, Chao; Ren, Dongren; Chen, Guo-Yun

    2016-06-03

    Sepsis is one of the leading causes of death worldwide. Although the prevailing theory for the sepsis syndrome is a condition of uncontrolled inflammation in response to infection, sepsis is increasingly being recognized as an immunosuppressive state known as endotoxin tolerance. We found sialylation of cell surface was significantly increased on LPS-induced tolerant cells; knockdown of Neu1 in macrophage cell line RAW 264.7 cells resulted in enhanced LPS-induced tolerance, whereas overexpression of Neu1 or treatment with sialidase abrogated LPS-induced tolerance, as defined by measuring TNF-α levels in the culture supernatants. We also found that the expression of Siglec-1 (a member of sialic acid-binding Ig (I)-like lectin family members, the predominant sialic acid-binding proteins on cell surface) was specifically up-regulated in endotoxin tolerant cells and the induction of Siglec-1 suppresses the innate immune response by promoting TGF-β1 production. The enhanced TGF-β1 production by Siglec-1 was significantly attenuated by spleen tyrosine kinase (Syk) inhibitor. Knockdown of siglec-1 in RAW 264.7 cells resulted in inhibiting the production of TGF-β1 by ubiquitin-dependent degradation of Syk. Mechanistically, Siglec-1 associates with adaptor protein DNAX-activation protein of 12 kDa (DAP12) and transduces a signal to Syk to control the production of TGF-β1 in endotoxin tolerance. Thus, Siglec-1 plays an important role in the development of endotoxin tolerance and targeted manipulation of this process could lead to a new therapeutic opportunity for patients with sepsis.

  10. Use of CTLA4Ig for induction of mixed chimerism and renal allograft tolerance in nonhuman primates.

    Science.gov (United States)

    Yamada, Y; Ochiai, T; Boskovic, S; Nadazdin, O; Oura, T; Schoenfeld, D; Cappetta, K; Smith, R-N; Colvin, R B; Madsen, J C; Sachs, D H; Benichou, G; Cosimi, A B; Kawai, T

    2014-12-01

    We have previously reported successful induction of renal allograft tolerance via a mixed chimerism approach in nonhuman primates. In those studies, we found that costimulatory blockade with anti-CD154 mAb was an effective adjunctive therapy for induction of renal allograft tolerance. However, since anti-CD154 mAb is not clinically available, we have evaluated CTLA4Ig as an alternative agent for effecting costimulation blockade in this treatment protocol. Two CTLA4Igs, abatacept and belatacept, were substituted for anti-CD154 mAb in the conditioning regimen (low dose total body irradiation, thymic irradiation, anti-thymocyte globulin and a 1-month posttransplant course of cyclosporine [CyA]). Three recipients treated with the abatacept regimen failed to develop comparable lymphoid chimerism to that achieved with anti-CD154 mAb treatment and these recipients rejected their kidney allografts early. With the belatacept regimen, four of five recipients developed chimerism and three of these achieved long-term renal allograft survival (>861, >796 and >378 days) without maintenance immunosuppression. Neither chimerism nor long-term allograft survival were achieved in two recipients treated with the belatacept regimen but with a lower, subtherapeutic dose of CyA. This study indicates that CD28/B7 blockade with belatacept can provide a clinically applicable alternative to anti-CD154 mAb for promoting chimerism and renal allograft tolerance.

  11. Prevalence of diabetes mellitus and impaired glucose tolerance in patients with decompensated cirrhosis being evaluated for liver transplantation: the utility of oral glucose tolerance test

    Directory of Open Access Journals (Sweden)

    Ana Carolina Costa Bragança

    2010-03-01

    Full Text Available CONTEXT: Cirrhosis, diabetes mellitus, impaired glucose tolerance, insulin resistance, and protein calorie malnutrition are important issues in cirrhotic patients because they can increase the progression of liver disease and worsen its prognosis. OBJECTIVE:To determine the prevalence of diabetes mellitus, impaired glucose tolerance and insulin resistance in cirrhotic patients being evaluated for liver transplantation and their impacts on a 3-month follow-up, and to compare fasting glycemia and oral glucose tolerance test. METHODS: A cross-sectional study was performed in consecutively included adult patients. Diabetes mellitus was established through fasting glycemia and oral glucose tolerance test in diagnosing diabetes mellitus in this population. HOMA-IR and HOMA-β indexes were calculated, and nutritional assessment was performed by subjective global assessment, anthropometry and handgrip strength through dynamometry. RESULTS: Diabetes mellitus was found in 40 patients (64.5%, 9 (22.5% of them by fasting glycemia and 31 (77.5% of them by oral glucose tolerance test. Insulin resistance was found in 40 (69% of the patients. There was no relationship between diabetes mellitus and the etiology of cirrhosis. Protein calorie malnutrition was diagnosed in a range from 3.22% to 45.2% by anthropometry, 58.1% by subjective global assessment and 88.7% by handgrip strength. Diabetes mellitus identified by oral glucose tolerance test was related significantly to a higher prevalence of infectious complications and deaths in a 3-month period (P = 0.017. CONCLUSION: The prevalence of diabetes mellitus, impaired glucose tolerance, insulin resistance and protein calorie malnutrition is high in cirrhotic patients on the waiting list for liver transplantation. There were more infectious complications and/or deaths in a 3-month follow-up period in patients with diabetes mellitus diagnosed by oral glucose tolerance test. Oral glucose tolerance test seems to be

  12. Induction

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Elkjaer, Bente

    2010-01-01

    The purpose of this paper is to explore how induction of newcomers can be understood as both organizational renewal and the maintenance of status quo, and to develop ways of describing this in terms of learning.......The purpose of this paper is to explore how induction of newcomers can be understood as both organizational renewal and the maintenance of status quo, and to develop ways of describing this in terms of learning....

  13. Induction of desiccation tolerance in plant somatic embryos : how exclusive is the protective role of sugars?

    NARCIS (Netherlands)

    Hoekstra, F.A.; Golovina, E.A.; Tetteroo, F.A.A.; Wolkers, W.F.

    2001-01-01

    Plant somatic embryos usually lack desiccation tolerance. They may acquire such a tolerance upon preculture in the presence of abscisic acid (ABA), followed by slow drying, but not fast drying. ABA causes torpedo-shaped somatic embryos to lose their chlorophyll, suspend growth, exhibit low rates of

  14. Comparison of efficacy, tolerability, and cost of newer with conventional oral iron preparation

    Directory of Open Access Journals (Sweden)

    S.S. Patil

    2013-01-01

    Full Text Available Background: Iron deficiency anaemia in women of reproductive age group is a major health problem in India. Objective: The present study was designed to compare the efficacy, tolerability, and cost, of three oral iron preparations among the anaemic pregnant women (n=6o of gestation (12-24 weeks. Methodology: The patients were divided into 3 groups (n=20 and treated with ferrous fumarate(100mg, ferrous bisglycinate (100mg,and carbonyl iron(100mg respectively. Follow-up was done for 3 months. Haemoglobin gm%, mean corpuscular volume and reticulocyte count were assessed at 0,1,2,3 months and serum ferritin at 0 and 3 months. Adverse effects were monitored and cost analysis was done at end of three months. Results: Significant increase in Hb was seen in all three groups (p<0.001 but, no significant difference was found between three treatments in relation to increase in Hb. Increase in ferritin with ferrous fumarate was significantly more than other treatments (p<0.05. Nausea, vomiting, epigastric pain was significantly more with ferrous fumarate but patient compliance was not affected due to them. Ferrous fumarate was the cheapest amongst all three treatments. Conclusion: It can be concluded that, ferrous fumarate still can be considered best cost effective medication with tolerable side effects for treatment as well as prevention of iron deficiency anaemia in pregnancy.

  15. An elevated 1-h post- load glucose level during the oral glucose tolerance test detects prediabetes.

    Science.gov (United States)

    Buysschaert, Martin; Bergman, Michael; Yanogo, Donald; Jagannathan, Ram; Buysschaert, Benoit; Preumont, Vanessa

    The objective of the study was to compare the diagnosis of dysglycemic states by conventional oral glucose tolerance test (OGTT) criteria (fasting and 2-h plasma glucose) with the 1-h post-load plasma glucose level. 34 individuals (mean age: 55±13years; BMI: 27.7±6.3kg/m(2)) at risk for prediabetes were administered a 75g OGTT. Individuals with normal glucose tolerance (NGT) or prediabetes were identified according to fasting and/or 2-h plasma glucose (PG) concentrations. Subsequently, subjects were divided in 2 groups: group 1 (n=21) with a 1-h PGh PG≥155mg/dl. HOMA was performed to assess β-cell function and insulin sensitivity. NGT or prediabetes based on conventional criteria correlated with the 1-h PGh PG≥155mg/dl was associated with higher HbA1c levels (6.1±0.5 vs. 5.5±0.3%, ph PGh post-load plasma glucose value ≥155mg/dl is strongly associated with conventional criteria for (pre)diabetes and alterations of β-cell function. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  16. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    Science.gov (United States)

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 7.8 and 11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of 2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  17. Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

    Directory of Open Access Journals (Sweden)

    Maristela Ruberti

    2012-01-01

    Full Text Available In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs from small intestine of transgenic (TGN DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β+ T-cell subset in IELs of TGN. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

  18. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  19. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  20. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    Science.gov (United States)

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice.

  1. Reduction of Factor VIII Inhibitor Titers During Immune Tolerance Induction With Recombinant Factor VIII-Fc Fusion Protein.

    Science.gov (United States)

    Groomes, Charles L; Gianferante, David M; Crouch, Gary D; Parekh, Dina S; Scott, David W; Lieuw, Kenneth

    2016-05-01

    The development of inhibitors toward factor VIII (FVIII) is a common and serious complication of hemophilia A (HA) therapy. Patients with hemophilia who develop inhibitors often undergo time- and resource-intensive immune tolerance induction (ITI) protocols. We report a 15-month-old male with severe HA and a high-titer inhibitor that occurred while receiving prophylactic treatment with recombinant FVIII (rFVIII), in whom significant inhibitor titer reduction was achieved with thrice weekly infusions of a new, prolonged half-life rFVIII-Fc fusion protein product (trade name Eloctate). Further studies are warranted to explore the potential of Eloctate in ITI protocols.

  2. Arsenate tolerance mechanism of Oenothera odorata from a mine population involves the induction of phytochelatins in roots.

    Science.gov (United States)

    Kim, Dae-Yeon; Park, Hyun; Lee, Sang-Hwan; Koo, Namin; Kim, Jeong-Gyu

    2009-04-01

    We investigated the arsenate tolerance mechanisms of Oenothera odorata by comparing two populations [i.e., one population from the mine site (MP) and the other population from an uncontaminated site (UP)] via the exposure of hydroponic solution containing arsenate (i.e., 0-50 microM). The MP plants were significantly more tolerant to arsenate than UP plants. The UP plants accumulated more As in their shoots and roots than did the MP plants. The UP plants translocated up to 21 microg g(-1) of As into shoots, whereas MP plants translocated less As (up to 4.5 microg g(-1)) to shoots over all treatments. The results of lipid peroxidation indicated that MP plants were less damaged by oxidative stress than were UP plants. Phytochelatin (PC) content correlated linearly with root As concentration in the MP (i.e., [PCs](root)=1.69x[As](root), r(2)=0.945) and UP (i.e., [PCs](root)=0.89x[As](root), r(2)=0.979) plants. This relationship means that increased PC to As ratio may be associated with increased tolerance. Our results suggest that PC induction in roots plays a critical role in As tolerance of O. odorata.

  3. Suppression of EAE by oral tolerance is independent of endogenous IFN-beta whereas treatment with recombinant IFN-beta ameliorates EAE

    DEFF Research Database (Denmark)

    Liu, Yawei; Teige, Ingrid; Ericsson, Ida

    2010-01-01

    IFN-beta is anticipated to have an important function in mucosal tolerance, as it is one of the major cytokines produced by plasmacytoid dendritic cells, and has recently been suggested as central to the maintenance of mucosal homeostasis. Here, we have investigated whether oral tolerance is depe......, however this was not a prerequisite for establishment of oral tolerance.Immunology and Cell Biology advance online publication, 12 January 2010; doi:10.1038/icb.2009.111....

  4. Severe oral infection due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia.

    Science.gov (United States)

    Ishihara, Yuko; Kanda, Junya; Tanaka, Kaori; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Yamazaki, Rie; Kako, Shinichi; Nishida, Junji; Watanabe, Kunitomo; Kanda, Yoshinobu

    2014-12-01

    We report a case of severe oral infection with a high fever due to Lactobacillus rhamnosus during induction chemotherapy for acute myeloid leukemia. The patient did not improve on treatment with meropenem, clindamycin, or vancomycin until neutrophil recovery. Since L. rhamnosus GG is used in dairy products, and the patient ingested dairy products daily before starting chemotherapy, we suspected an association between the ingestion of dairy products and the development of infection. Pulsed-field gel electrophoresis using two different restriction enzymes showed that the strain isolated from the patient was identical to the L. rhamnosus GG strain isolated from dairy products and ATCC #53103. This was confirmed by a PCR assay with species-specific L. rhamnosus GG primers. Since Lactobacillus infection, particularly L. rhamnosus infection, can be fatal in immunocompromised hosts, we should consider Lactobacillus as a causative organism when Gram-positive rods are detected during treatment with broad-spectrum antibiotics and vancomycin. The causal association between the ingestion of dairy products containing Lactobacillus and Lactobacillus infection in immunocompromised hosts warrants further study.

  5. Type I interferon signalling is not required for the induction of endotoxin tolerance.

    Science.gov (United States)

    Karimi, Yalda; Poznanski, Sophie M; Vahedi, Fatemeh; Chen, Branson; Chew, Marianne V; Lee, Amanda J; Ashkar, Ali A

    2017-02-08

    Endotoxin, or LPS tolerance, is an immunomodulatory mechanism that results in a significantly diminished response to secondary LPS exposure, which may serve to protect the host against endotoxic shock. Type I interferons (IFNs) are cytokines released upon LPS binding to TLR4 and have been shown to have immunomodulatory properties. Due to this regulatory function of type I IFN, we aimed to investigate the role of type I IFN signalling in LPS tolerance. Our data suggests that type I IFN does not play a role in LPS tolerance in vitro, as both wild type and IFNAR1(-/-) peritoneal macrophages showed reduced cytokine production after secondary LPS exposure. Furthermore, both wild type and IFNAR1(-/-) mice were protected from a lethal dose of LPS after receiving three small doses to induce tolerance. However, IFNAR(-/-) mice seemed to recover faster than wild type mice, suggesting type I IFN signalling plays a detrimental role in LPS-induced sepsis. Although type I IFN may have a regulatory function in microbial infections, it does not seem to play a role in endotoxin tolerance. Type I IFN involvement in bacterial infection remains complex and further studies are needed to define the regulatory function of type I IFN signalling.

  6. Value of oral glucose tolerance test in the acute phase of myocardial infarction

    Directory of Open Access Journals (Sweden)

    Grabczewska Zofia

    2011-03-01

    Full Text Available Abstract Background Although European guidelines advise oral glucose tolerance test (OGTT in patients with acute myocardial infarction (AMI before or shortly after hospital discharge, data supporting this recommendation are inconclusive. We aimed to analyze whether disturbances in glucose metabolism diagnosed before hospital discharge in AMI patients represents a latent pre-existing condition or rather temporary finding. Additionally, we planned to investigate the value of pre-selected glycemic control parameters as predictors of long-term glucometabolic state. Methods We assessed admission glycemia, glycated hemoglobin, mean blood glucose concentration on days 1 and 2 in 200 patients with a first AMI but without overt disturbances of glucose metabolism. We also performed OGTT at discharge and 3 months after discharge. Results The prevalence of disturbances in glucose metabolism (as assessed by OGTT at 3 months was significantly lower than at discharge (29% vs. 48%, p = 0.0001. Disturbances in glucose metabolism were not confirmed in 63% of patients with impaired glucose tolerance and in 36% of patients with diabetes mellitus diagnosed during the acute phase of AMI. Age >77 years, glucose ≥12.06 mmol/l at 120 minutes during OGTT before discharge and mean blood glucose level on day 2 >7.5 mmol/l were identified as independent predictors of disturbances in glucose metabolism at the 3-month follow-up. Conclusions Disturbances in glucose metabolism observed in patients with a first AMI are predominantly transient. Elderly age, high plasma glucose concentration at 120 minutes during OGTT at discharge and elevated mean blood glucose level on day 2 were associated with sustained disturbances in glucose metabolism.

  7. Efficacy and tolerability of high oral doses of levetiracetam in children with epilepsy.

    Science.gov (United States)

    Obeid, Makram; Pong, Amanda W

    2010-09-01

    Despite the advent of new antiepileptic drugs, many children continue to have refractory seizures. We sought to determine whether oral LEV is helpful in seizure control and tolerable at doses higher than 60mg/kg/day in the pediatric outpatient population. A retrospective chart review over a 1.5-year period was performed at the Columbia Comprehensive Epilepsy Center to identify children who were treated with levetiracetam doses titrated above the usual 40-60mg/kg/day. Data was collected on seizure semiology, epilepsy type, seizure frequency, concomitant antiepileptic drugs, and adverse effects. Thirty-two children, ranging in age from 1 to 19 years, required high dose levetiracetam. The median dosage of levetiracetam was 146mg/kg/day (range, 70-275mg/kg/day), and the median maximum serum trough level was 43mcg/ml (range, 20-121mcg/ml). All but one patient were taking one or more other antiepileptic drugs. A more than 50% reduction in seizure frequency was observed in 14 children (44%), with 5 achieving seizure freedom (16%). No response to high dose levetiracetam was found in 14 children (44%), and worsening of seizure frequency occurred in 4 (12%). Adverse effects were observed in 4 patients (12%), and were behavioral. Not only do some children tolerate high doses and serum levels of levetiracetam, but they may also benefit from them, suggesting that doses higher than 60mg/kg/day may be considered in children who partially respond to the lower doses. Copyright 2010 Elsevier B.V. All rights reserved.

  8. The oral glucose tolerance test is frequently abnormal in patients with uncontrolled epilepsy.

    Science.gov (United States)

    Vianna, J B M; Atallah, A N; Prado, G F; Valente, O; Duarte-Barros, M L; Vianna, E C S; Mello, L E A M

    2006-08-01

    The clinical efficacy of the ketogenic diet as therapy for patients with difficult-to-treat epilepsy prompted us to investigate the glucose metabolism of these patients under an oral overload of glucose, that is, in the oral glucose tolerance test (OGTT). Thirty patients (12 males, 18 females; age range: 17-59, mean: 35.1) with difficult-to-treat epilepsy, 23 patients with controlled epilepsy (11 males, 12 females; age range: 14-66, mean: 36.9), and 39 control subjects (18 males, 21 females; age range: 16-58, mean: 33.3) were evaluated with the OGTT. For patients with epilepsy, we also measured C-peptide and glycosylated hemoglobin in the fasting state. Glucose levels lower than 70 mg/dL at any point of the curve were considered to be abnormal. All subjects in the control group and the group with controlled epilepsy had a normal OGTT. In contrast, all 30 patients with difficult-to-treat epilepsy had at least one point on the OGTT curve below the normal range (Poral glucose load (Pepilepsy as compared with the group with controlled epilepsy. Fasting glycohemoglobin and insulin levels did not differ between the two patient groups. We suggest that undiagnosed metabolic disturbances in patients with difficult-to-treat epilepsy may somehow contribute to their refractoriness to conventional pharmacological therapy. We propose the hypothesis that calorie-restricted diets aimed at correcting OGTT curves may prove beneficial in treating patients with difficult-to-treat epilepsy. Our hypothesis generates a clear endpoint for the diet, and its demonstration would provide new standards for diet-based antiepileptic regimens. Accordingly, our results may help in understanding the positive consequences of ketogenic or calorie-restricted diets in persons with seizures.

  9. Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure.

    Science.gov (United States)

    Ménard, Sandie; Ben Haddou, Tanila; Ramadani, Arba Pramundita; Ariey, Frédéric; Iriart, Xavier; Beghain, Johann; Bouchier, Christiane; Witkowski, Benoit; Berry, Antoine; Mercereau-Puijalon, Odile; Benoit-Vical, Françoise

    2015-10-01

    Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia threatens global malaria control strategies. Whether delayed parasite clearance, which exposes larger parasite numbers to artemisinins for longer times, selects higher-grade resistance remains unexplored. We investigated whether long-lasting artemisinin pressure selects a novel multidrug-tolerance profile. Although 50% inhibitory concentrations for 10 antimalarial drugs tested were unchanged, drug-tolerant parasites showed higher recrudescence rates for endoperoxides, quinolones, and an antifolate, including partner drugs of recommended combination therapies, but remained susceptible to atovaquone. Moreover, the age range of intraerythrocytic stages able to resist artemisinin was extended to older ring forms and trophozoites. Multidrug tolerance results from drug-induced quiescence, which enables parasites to survive exposure to unrelated antimalarial drugs that inhibit a variety of metabolic pathways. This novel resistance pattern should be urgently monitored in the field because this pattern is not detected by current assays and represents a major threat to antimalarial drug policy.

  10. Early induction of Fe-SOD gene expression is involved in tolerance to Mn toxicity in perennial ryegrass.

    Science.gov (United States)

    Ribera-Fonseca, Alejandra; Inostroza-Blancheteau, Claudio; Cartes, Paula; Rengel, Zed; Mora, M L

    2013-12-01

    Manganese (Mn) toxicity limits plant growth in acid soils. Although Mn toxicity induces oxidative stress, the role of superoxide dismutase (SOD, EC.1.15.1.1) isoforms in conferring Mn tolerance remains unclear. Seedlings of ryegrass cultivars Nui (Mn-sensitive) and Kingston (Mn-tolerant) were hydroponically grown at 2.4 (optimal) or 750 μM Mn (toxic) concentration, and harvested from 2 to 48 h. Kingston showed higher shoot Mn than Nui at 2.4 μM Mn. At toxic supply, shoot Mn concentration steadily increased in both cultivars, with Kingston having the highest accumulation at 48 h. An early (2 h) increase in lipid peroxidation under Mn excess occurred, but it returned (after 6 h) to the basal level in Kingston only. Kingston exhibited higher SOD activity than Nui, and that difference increased due to toxic Mn. In general, Mn-induced gene expression of Mn- and Cu/Zn-SOD isoforms was higher in Nui than Kingston. Nevertheless, under Mn excess, we found a greater Fe-SOD up-regulation (up to 5-fold) in Kingston compared to Nui. Thus, Fe-SOD induction in Kingston might explain, at least partly, its high tolerance to Mn toxicity. This is the first evidence that Mn toxicity causes differential gene expression of SOD isoforms in ryegrass cultivars in the short-term.

  11. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice

    DEFF Research Database (Denmark)

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-01-01

    were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured...... in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine...

  12. Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance

    DEFF Research Database (Denmark)

    Rask, E; Olsson, T; Söderberg, S;

    2004-01-01

    Subjects with impaired glucose tolerance (IGT) are usually overweight and exhibit insulin resistance with a defective compensation of insulin secretion. In this study, we sought to establish the interrelation between insulin secretion and insulin sensitivity after oral glucose in non-obese subjects......). Plasma levels of GLP-1 and GIP increased after oral glucose. Total secretion of these incretin hormones during the 3-hour test did not differ between the 2 groups. However, the 30-minute increase in GLP-1 concentrations was lower in IGT than in NGT (P =.036). We conclude that also in non-obese subjects...

  13. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction.

    Science.gov (United States)

    Yen, Ching-Yu; Chiu, Chien-Chih; Haung, Rou-Wen; Yeh, Chi-Chen; Huang, Kuang-Jing; Chang, Kuo-Feng; Hseu, You-Cheng; Chang, Fang-Rong; Chang, Hsueh-Wei; Wu, Yang-Chang

    2012-09-18

    Goniothalamin (GTN), a plant bioactive styryl-lactone, is a natural product with potent anti-tumorigenesis effects for several types of cancer. Nonetheless, the anticancer effect of GTN has not been examined in oral cancer. The present study was designed to evaluate its potential anticancer effects in an oral squamous cell carcinoma (OSCC) model and to determine the possible mechanisms with respect to apoptosis, DNA damage, reactive oxygen species (ROS) induction, and mitochondrial membrane potential. Our data demonstrated that cell proliferation was significantly inhibited by GTN in Ca9-22 OSCC cancer cells in concentration- and time-dependent manners (pGTN-treated Ca9-22 cancer cells, the sub-G1 population and annexin V-intensity significantly increased in a concentration-dependent manner (pGTN-treated Ca9-22 cancer cells in concentration-response relationship (pGTN significantly induced intracellular ROS levels in Ca9-22 cancer cells in a concentration- and time-dependent manner (pGTN-treated Ca9-22 cancer cells was significantly decreased in concentration- and time-dependent relationships (pGTN against oral cancer cells is valid and GTN-induced growth inhibition and apoptosis influence the downstream cascade including ROS induction, DNA damage, and mitochondria membrane depolarization. Therefore, GTN has potential as a chemotherapeutic agent against oral cancer.

  14. Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test

    DEFF Research Database (Denmark)

    Montelius, Caroline; Szwiec, Katarzyna; Kardas, Marek

    2014-01-01

    BACKGROUND & AIMS: Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose......, and decreased late postprandial secretion of ghrelin. CONCLUSION: Dietary thylakoids may be a novel agent in reducing the glycaemic responses to high carbohydrate and high glycaemic index foods. Thylakoids may in the future be promising for treatment and prevention of diabetes, overweight and obesity....... metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet. METHODS: Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1 g/kg d-glucose) was performed. The experiment was designed as a cross-over study...

  15. Induction of immune tolerance with heart-thymus composite allotransplantation in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Hai-bo; XIA Sui-sheng; WEN Hao; HUANG Zu-fa; YE Qi-fa

    2005-01-01

    Objective To study on the role of thymus transplantation for heart allograft in rats. Methods Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, level of IL-2, IL-4 and its mRNA expression in serum and cardiac grafts were investigated. Results Heart-thymus combined transplantation achieved effect in the prolongation of cardiac graft survival with short-term administration of cyclosporine. Conclusions Vascularized thymus transplantation induced immune tolerance in thymectomized rats.

  16. Induction of tolerance using Fas ligand: a double-edged immunomodulator.

    Science.gov (United States)

    Askenasy, Nadir; Yolcu, Esma S; Yaniv, Isaac; Shirwan, Haval

    2005-02-15

    Apoptosis mediated by Fas ligand (FasL) interaction with Fas receptor plays a pivotal regulatory role in immune homeostasis, immune privilege, and self-tolerance. FasL, therefore, has been extensively exploited as an immunomodulatory agent to induce tolerance to both autoimmune and foreign antigens with conflicting results. Difficulties associated with the use of FasL as a tolerogenic factor may arise from (1) its complex posttranslational regulation, (2) the opposing functions of different forms of FasL, (3) different modes of expression, systemic versus localized and transient versus continuous, (4) the level and duration of expression, (5) the sensitivity of target tissues to Fas/FasL-mediated apoptosis and the efficiency of antigen presentation in these tissues, and (6) the types and levels of cytokines, chemokines, and metalloproteinases in the extracellular milieu of the target tissues. Thus, the effective use of FasL as an immunomodulator to achieve durable antigen-specific immune tolerance requires careful consideration of all of these parameters and the design of treatment regimens that maximize tolerogenic efficacy, while minimizing the non-tolerogenic and toxic functions of this molecule. This review summarizes the current status of FasL as a tolerogenic agent, problems associated with its use as an immunomodulator, and new strategies to improve its therapeutic potential.

  17. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  18. The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats.

    Science.gov (United States)

    Paulo, Alexandra; Martins, Sofia; Branco, Pedro; Dias, Teresa; Borges, Carlos; Rodrigues, Ana Isabel; Costa, Maria do Céu; Teixeira, Adriano; Mota-Filipe, Hélder

    2008-04-01

    The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.

  19. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Vousden, M; Oliver, S; Johnson, M; Ward, C; Cheon, A; Choo, Y S; Kim, I

    2001-02-01

    Gemifloxacin mesylate (SB-265805-S, LB-20304a) is a potent, novel fluoroquinolone agent with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in two parallel group studies in healthy male volunteers after doses of 160, 320, 480, and 640 mg once daily for 7 days. Multiple serum or plasma and urine samples were collected on days 1 and 7 and were analyzed for gemifloxacin by high-performance liquid chromatography (HPLC)-fluorescence (study 1) or HPLC-mass spectrometry (study 2). Safety assessments included vital signs, 12-lead electrocardiogram (ECG) readings, hematology, clinical chemistry, urinalysis, and adverse experience monitoring. Gemifloxacin was rapidly absorbed, with a time to maximum concentration of approximately 1 h after dosing followed by a biexponential decline in concentration. Generally, maximum concentration and area under the concentration-time curve (AUC) increased linearly with dose after either single or repeat doses. Mean +/- standard deviation values of AUC(0-tau) on day 7 were 4.92 +/- 1.08, 9.06 +/- 2.20, 12.2 +/- 3.69, and 20.1 +/- 3.67 microg x h/ml following 160-, 320-, 480-, and 640-mg doses, respectively. The terminal-phase half-life was approximately 7 to 8 h, independent of dose, and was similar following single and repeated administrations. There was minimal accumulation of gemifloxacin after multiple dosing. Approximately 20 to 30% of the administered dose was excreted unchanged in the urine. The renal clearance was 160 ml/min on average after single and multiple doses, which was slightly greater than the accepted glomerular filtration rate (approximately 120 ml/min). These data show that the pharmacokinetics of gemifloxacin are linear and independent of dose. Gemifloxacin was generally well tolerated, although one subject was withdrawn from the study after 6 days at 640 mg for mild, transient elevations of alanine aminotransferase and aspartate

  20. Indirect effects of oral tolerance to ovalbumin interfere with the immune responses triggered by Schistosoma mansoni eggs

    Directory of Open Access Journals (Sweden)

    C.R. Carvalho

    2002-10-01

    Full Text Available The objective of the present study was to investigate whether the injection of a tolerated protein (indirect effects affects the formation of granulomas around Schistosoma mansoni eggs trapped in the lungs after intravenous (iv injection into normal (noninfected C57BL/6 mice (6 animals per group. To induce oral tolerance to chicken egg ovalbumin a 1/5 dilution of egg white in water was offered ad libitum in a drinking bottle for 3 days. Control mice received water. After 7 days, control and experimental animals were injected iv with 2,000 S. mansoni eggs through a tail vein. In some mice of both groups the iv injection of eggs was immediately followed by intraperitoneal (ip immunization with 10 µg of dinitrophenylated conjugates of ovalbumin (DNP-Ova emulsified in complete Freund's adjuvant (CFA or only CFA; 18 days later, mice were bled and killed by ether inhalation. The lungs were fixed in formalin and embedded in paraffin. Serial sections of 5 µm were stained with Giemsa, Gomori's silver reticulin and Sirius red (pH 10.2. Granuloma diameters were measured in histological sections previously stained with Gomori's reticulin. Anti-DNP and anti-soluble egg antigen (SEA antibodies were analyzed by ELISA. In mice orally tolerant to ovalbumin the concomitant ip injection of DNP-Ova resulted in significantly lower anti-SEA antibodies (ELISA*: 1395 ± 352 in non-tolerant and 462 ± 146 in tolerant mice and affected granuloma formation around eggs, significantly decreasing granuloma size (area: 22,260 ± 2478 to 12,993 ± 3242 µm². Active mechanisms triggered by injection of tolerated antigen (ovalbumin reduce granuloma formation.

  1. Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers.

    Science.gov (United States)

    Allen, A; Bygate, E; Oliver, S; Johnson, M; Ward, C; Cheon, A J; Choo, Y S; Kim, I C

    2000-06-01

    Gemifloxacin (known as SB-265805 or LB-20304) is a potent, novel fluoroquinolone compound with a broad spectrum of antibacterial activity. The pharmacokinetics and tolerability of oral gemifloxacin were characterized in healthy male volunteers after a single dose of 20, 40, 80, 160, 320, 600, or 800 mg. Multiple serum and urine samples were collected and analyzed for gemifloxacin using high-performance liquid chromatography with fluorescence detection. Safety assessments included vital signs, 12-lead electrocardiogram readings, hematology, clinical chemistry, urinalysis, and adverse-experience monitoring. Gemifloxacin was rapidly absorbed after all doses. Maximum concentrations of gemifloxacin in serum (C(max)) were achieved approximately 1 h after dosing, after which concentrations in serum declined in a biexponential manner. Values of C(max) and the area under the concentration-time curve in serum from 0 h to infinity (serum AUC(0-infinity)) increased linearly with dose. Serum AUC(0-infinity) values (mean +/- standard deviation) were 0.65+/-0.01, 1.28+/-0.22, 2.54+/-0.31, 5.48+/-1.24, 9.82+/-2.70, 24.4+/-7.1, and 31.4+/-7.6 microg. h/ml following 20-, 40-, 80-, 160-, 320-, 600-, and 800-mg doses, respectively. The terminal phase elimination half-life was independent of dose, with an overall mean of 7.4+/-2.0 h. The profiles indicated that the pharmacokinetic profile is suitable for a once-daily dosing regimen. Approximately 25 to 40% of the administered dose was excreted unchanged in the urine, and renal clearance (ca. 150 ml/min) was independent of dose. There were no significant changes in clinical chemistry, hematology, or urinalysis parameters, vital signs, or 12-lead electrocardiogram readings in subjects, irrespective of dose. The results of these studies support the further investigation of once-daily administration of gemifloxacin.

  2. The Thymic Orchestration Involving Aire, miRNAs, and Cell-Cell Interactions during the Induction of Central Tolerance.

    Science.gov (United States)

    Passos, Geraldo Aleixo; Mendes-da-Cruz, Daniella Arêas; Oliveira, Ernna Hérida

    2015-01-01

    Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs). These cells ectopically express a vast set of peripheral tissue antigens (PTAs), a property termed promiscuous gene expression that is associated with the presentation of PTAs by mTECs to thymocytes. Thymocyte clones that have a high affinity for PTAs are eliminated by apoptosis in a process termed negative selection, which is essential for tolerance induction. The Aire gene is an important factor that controls the expression of a large set of PTAs. In addition to PTAs, Aire also controls the expression of miRNAs in mTECs. These miRNAs are important in the organization of the thymic architecture and act as posttranscriptional controllers of PTAs. Herein, we discuss recent discoveries and highlight open questions regarding the migration and interaction of developing thymocytes with thymic stroma, the ectopic expression of PTAs by mTECs, the association between Aire and miRNAs and its effects on central tolerance.

  3. Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance.

    Science.gov (United States)

    Hubert, François-Xavier; Kinkel, Sarah A; Davey, Gayle M; Phipson, Belinda; Mueller, Scott N; Liston, Adrian; Proietto, Anna I; Cannon, Ping Z F; Forehan, Simon; Smyth, Gordon K; Wu, Li; Goodnow, Christopher C; Carbone, Francis R; Scott, Hamish S; Heath, William R

    2011-09-01

    To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter. Aire deficiency reduced the number of mature single-positive OVA-specific CD4(+) or CD8(+) T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways to OVA-dependent negative selection depending on the T-cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to medullary thymic epithelial cell (mTEC)-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTECs can mediate tolerance by direct presentation of Aire-regulated antigens to both CD4 and CD8 T cells.

  4. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens

    NARCIS (Netherlands)

    C.B.M. Maassen (Kitty); J.D. Laman (Jon); C. van Holten-Neelen; L. Hoogteijling (L.); L. Groenewegen (Lizet); L. Visser (Lizette); M.M. Schellekens (M.); W.G. Boersma (Wim); H.J.H.M. Claassen (Eric)

    2003-01-01

    textabstractOral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we

  5. Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing meyelin antigens

    NARCIS (Netherlands)

    Maassen, C.B.M.; Holten-Neelen, van J.C.P.A.; Groenewegen, L.; Hoogteijling, L.; Visser, L.; Boersma, W.J.A.

    2003-01-01

    Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetica

  6. An improved fault tolerant for a five-phase induction machine under open gate transistor faults

    Directory of Open Access Journals (Sweden)

    Elhussien A. Mahmoud

    2016-09-01

    Full Text Available Of the different outstanding merits of multiphase machines is their ability to run steadily with some phases open. Commonly, optimal current control (OCC to remaining healthy phases is usually engaged to ensure a certain optimization criterion. Most of the available literature investigates the fault case where one of the motor phases is completely disconnected due to a failure in one of the inverter legs. To maintain pre-fault operating conditions, the machine experiences a 53% increase in the total copper loss; otherwise, the machine should be deloaded. Under open gate fault condition of one of the upper or lower switching devices, the corresponding switch will be open, while the other switch in the same leg can be still used to enhance the machine performance under this case. This paper proposes an improved control strategy to optimize a five-phase induction motor drive under a gate failure of one of the inverter switching devices using a half cycle optimal current control (HCOCC technique. When compared with a conventional OCC, the proposed controller can effectively reduce the excessive copper loss by 50%, improve efficiency, and decrease the corresponding derating factor. The proposed controller is verified using a five-phase induction machine based on a simulation case study using MATLAB/SIMULINK.

  7. Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model.

    Science.gov (United States)

    Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre; Katz, Nathan; Zhu, Yanqing; Lin, Gloria; Choa, Ruth; Bagel, Jessica; O'Donnell, Patricia; Fitzgerald, Caitlin A; Langan, Therese; Wang, Ping; Casal, Margret L; Haskins, Mark E; Wilson, James M

    2016-09-01

    High fidelity animal models of human disease are essential for preclinical evaluation of novel gene and protein therapeutics. However, these studies can be complicated by exaggerated immune responses against the human transgene. Here we demonstrate that dogs with a genetic deficiency of the enzyme α-l-iduronidase (IDUA), a model of the lysosomal storage disease mucopolysaccharidosis type I (MPS I), can be rendered immunologically tolerant to human IDUA through neonatal exposure to the enzyme. Using MPS I dogs tolerized to human IDUA as neonates, we evaluated intrathecal delivery of an adeno-associated virus serotype 9 vector expressing human IDUA as a therapy for the central nervous system manifestations of MPS I. These studies established the efficacy of the human vector in the canine model, and allowed for estimation of the minimum effective dose, providing key information for the design of first-in-human trials. This approach can facilitate evaluation of human therapeutics in relevant animal models, and may also have clinical applications for the prevention of immune responses to gene and protein replacement therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Serratia entomophila bet gene induction and the impact of glycine betaine accumulation on desiccation tolerance.

    Science.gov (United States)

    Sheen, T R; O'Callaghan, M; Smalley, D J; Ronson, C W; Hurst, M R H

    2013-02-01

    The genes involved in choline transport and oxidation to glycine betaine in the biopesticidal bacterium Serratia entomophila were characterized, and the potential of osmoprotectants, coupled with increased NaCl concentrations, to improve the desiccation tolerance of this species was investigated. Serratia entomophila carries sequences similar to the Escherichia coli betTIBA genes encoding a choline transporter and dehydrogenase, a betaine aldehyde dehydrogenase and a regulatory protein. Disruption of betA abolished the ability of Ser. entomophila to utilize choline as a carbon source. Quantitative reverse-transcriptase PCR analysis revealed that betA transcription was reduced compared to that of the upstream genes in the operon, and that NaCl and choline induced bet gene expression. Glycine betaine and choline increased the NaCl tolerance of Ser. entomophila, and osmotically preconditioned cultures survived better than control cultures following desiccation and immediately after application to agricultural soil. Addition of glycine betaine and NaCl to growth medium can greatly enhance the desiccation survival of Ser. entomophila, and its initial survival in soil. Serratia entomophila is sensitive to desiccation and does not persist under low soil moisture conditions. Techniques described here for enhancing the desiccation survival of Ser. entomophila can be used to improve formulations of this bacterium, and allow its application under a wider range of environmental conditions. © 2012 AgResearch.

  9. Randomized clinical trial between hourly titrated and 2 hourly static oral misoprostol solution for induction of labor.

    Science.gov (United States)

    Rouzi, Abdulrahim A; Alsahly, Nora; Alamoudi, Rana; Almansouri, Nisma; Alsinani, Nawal; Alkafy, Souzan; Rozzah, Rayyan; Abduljabbar, Hassan

    2017-04-01

    Misoprostol is an effective agent for the induction of labor. Existing guidelines recommend oral misoprostol solution 25 μg every 2 hours. However, more research is required to optimize the use of oral misoprostol solution for the induction of labor. The purpose of this study was to compare efficacy and safety of hourly titrated-dose oral misoprostol solution with static-dose oral misoprostol solution every 2 hours for labor induction. In this randomized controlled study, oral misoprostol solution was administered as (1) 20 μg hourly (≤4 doses) that was increased in the absence of regular uterine contractions to 40 μg hourly (≤4 doses) and then to 60 μg hourly (≤16 doses) or (2) 25 μg every 2 hours until active labor began (≤12 doses). A sample size of 146 women was planned with the use of a projected 95% rate for the primary endpoint (vaginal delivery within 24 hours) for hourly titrated-dose misoprostol and 80% rate for static-dose misoprostol every 2 hours. Safety outcomes included maternal morbidity and adverse neonatal outcomes. From December 2013 to July 2015, 146 women were assigned randomly to treatment. Demographic and clinical factors were similar between groups, except for age. Vaginal delivery was achieved within 24 hours in 47 women (64.4%) who received hourly titrated-doses of misoprostol solution and 48 women (65.8%) who received 2-hourly static-dose misoprostol solution (P=1.00). Rates of vaginal delivery within 24 hours did not differ significantly between treatment groups for women who were nulliparous (P=1.00) or who had postterm pregnancies (P=.66), a Bishop score of ≤3 (P=.84), or oxytocin augmentation (P=.83). Cesarean deliveries were performed within 24 hours in 9 women who received hourly titrated-dose misoprostol solution and 2 women who received 2-hourly static-dose misoprostol solution (P=.056). Pyrexia and meconium-stained liquor occurred more frequently with the hourly titrated-dose regimen. The static-dose oral

  10. Prueba oral de tolerancia al almidón del grano de avena en ponies (Oral oats grain starch tolerance test in ponies

    Directory of Open Access Journals (Sweden)

    Perrone, G.

    2011-10-01

    Full Text Available ResumenSe efectuó una Prueba Oral de Tolerancia al Almidón del grano de Avena en ponies, para desarrollar una curva de glucemia propia de estas razas, compararla con las curvas de glucemia de equinos de mayor alzada, consumiendo pasturas o dietas mixtas de forrajes y concentrados, y observar si algún pony pudiera ser considerado unvalor atípico.SummaryAn oral oats grain starch tolerance test in ponies was carried out to develop a glycaemic curve specific to these breeds, compared it with glycaemic curves of larger height horses, pasture fed or forage and concentrates fed, and see if any pony could be considered outlier.

  11. Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Ruth E.Rosenstein; Diego C.Fernandez

    2014-01-01

    Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti-nopathy have focused either on highly speciifc therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis-tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch-emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.

  12. Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

    Science.gov (United States)

    Kumakura, Atsushi; Shikuma, Junpei; Ogihara, Norikazu; Eiki, Jun-ichi; Kanazawa, Masao; Notoya, Yōko; Kikuchi, Masatoshi; Odawara, Masato

    2013-01-01

    The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

  13. Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways

    Directory of Open Access Journals (Sweden)

    Jian Tan

    2016-06-01

    Full Text Available The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103+ dendritic cells (DCs, which promote differentiation of regulatory T (Treg cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs, particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103+ DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103+ DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens.

  14. Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

    Directory of Open Access Journals (Sweden)

    Natarajan Sudha

    2010-11-01

    Full Text Available Abstract Background Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components in order to ameliorate asthma-like, allergic pulmonary inflammation. Methods We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL and lung homogenate (LH were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy. Results CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03. Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41. This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007 and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017. The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0

  15. Induction of Tolerance to Cardiac Allografts Using Donor Splenocytes Engineered to Display on Their Surface an Exogenous FasL Protein1

    Science.gov (United States)

    Yolcu, Esma S.; Gu, Xiao; Lacelle, Chantale; Zhao, Hong; Bandura-Morgan, Laura; Askenasy, Nadir; Shirwan, Haval

    2008-01-01

    The critical role played by FasL in immune homeostasis renders this molecule as an attractive target for immunomodulation to achieve tolerance to auto and transplantation antigens. Immunomodulation with genetically modified cells expressing FasL was shown to induce tolerance to alloantigens. However, genetic modification of primary cells in a rapid, efficient, and clinically applicable manner proved challenging. Therefore, we tested the efficacy of donor splenocytes rapidly and efficiently engineered to display on their surface a chimeric form of FasL protein (SA-FasL) for tolerance induction to cardiac allografts. Intraperitoneal injection of ACI rats with WF splenocytes displaying SA-FasL on their surface resulted in tolerance to donor, but not F344 third party, cardiac allografts. Tolerance was associated with apoptosis of donor reactive T effector cells and induction/expansion of CD4+CD25+FoxP3+ T regulatory (Treg) cells. Treg cells played a critical role in the observed tolerance as adoptive transfer of sorted Treg cells from long-term graft recipients into naïve unmanipulated ACI rats resulted in indefinite survival of secondary WF grafts. Immunomodulation with allogeneic cells rapidly and efficiently engineered to display on their surface SA-FasL protein provides an effective and clinically applicable means of cell-based therapy with potential application to regenerative medicine, transplantation, and autoimmunity. PMID:18606644

  16. Changes of ghrelin following oral glucose tolerance test in obese children with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    Xiu-Min Wang; You-Jun Jiang; Li Liang; Li-Zhong Du

    2008-01-01

    AIM: To characterize changes in ghrelin levels in response to oral glucose tolerance test (OGTT) and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner I and Ⅱ stage with insulin resistance.METHODS: 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender: boys of Tanner I (BT-Ⅰ), boys of Tanner Ⅱ (BT- Ⅱ), girls of Tanner Ⅰ (GT-Ⅰ), girls of Tanner Ⅱ (GT-Ⅱ). Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 min following OGTT. The control children with normal BMI were divided into control boys of Tanner I (CBT-Ⅰ, n = 6), control boys of Tanner Ⅱ (CBT- Ⅱ, n = 5), control girls of Tanner I (CGT-1, n = 6), control girls of Tanner II (CGT- Ⅱ, n = 5). Fasting serum ghrelin levels were analyzed.RESULTS: Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage (CGT-Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT-Ⅰ vs CBT-n t = -4.794, P = 0.001). Basal ghrelin levels in BT- Ⅱ decreased more significantly than that in BT-Ⅰ group (t = 2.547, P = 0.029). Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT-Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in BT-Ⅰ (r = 0.898, P = 0.015). There wasn't a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance.CONCLUSION: In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance and insulin sensitivity.

  17. Vaccination strategies for Parkinson disease: induction of a swift attack or raising tolerance?

    Science.gov (United States)

    Romero-Ramos, Marina; von Euler Chelpin, Marianne; Sanchez-Guajardo, Vanesa

    2014-01-01

    Parkinson disease is the second most common neurodegenerative disease in the world, but there is currently no available cure for it. Current treatments only alleviate some of the symptoms for a few years, but they become ineffective in the long run and do not stop the disease. Therefore it is of outmost importance to develop therapeutic strategies that can prevent, stop, or cure Parkinson disease. A very promising target for these therapies is the peripheral immune system due to its probable involvement in the disease and its potential as a tool to modulate neuroinflammation. But for such strategies to be successful, we need to understand the particular state of the peripheral immune system during Parkinson disease in order to avoid its weaknesses. In this review we examine the available data regarding how dopamine regulates the peripheral immune system and how this regulation is affected in Parkinson disease; the specific cytokine profiles observed during disease progression and the alterations documented to date in patients' peripheral blood mononuclear cells. We also review the different strategies used in Parkinson disease animal models to modulate the adaptive immune response to salvage dopaminergic neurons from cell death. After analyzing the evidence, we hypothesize the need to prime the immune system to restore natural tolerance against α-synuclein in Parkinson disease, including at the same time B and T cells, so that T cells can reprogram microglia activation to a beneficial pattern and B cell/IgG can help neurons cope with the pathological forms of α-synuclein.

  18. Development of a native Escherichia coli induction system for ionic liquid tolerance.

    Directory of Open Access Journals (Sweden)

    Marijke Frederix

    Full Text Available The ability to solubilize lignocellulose makes certain ionic liquids (ILs very effective reagents for pretreating biomass prior to its saccharification for biofuel fermentation. However, residual IL in the aqueous sugar solution can inhibit the growth and function of biofuel-producing microorganisms. In E. coli this toxicity can be partially overcome by the heterologous expression of an IL efflux pump encoded by eilA from Enterobacter lignolyticus. In the present work, we used microarray analysis to identify native E. coli IL-inducible promoters and develop control systems for regulating eilA gene expression. Three candidate promoters, PmarR', PydfO', and PydfA', were selected and compared to the IPTG-inducible PlacUV5 system for controlling expression of eilA. The PydfA' and PmarR' based systems are as effective as PlacUV5 in their ability to rescue E. coli from typically toxic levels of IL, thereby eliminating the need to use an IPTG-based system for such tolerance engineering. We present a mechanistic model indicating that inducible control systems reduce target gene expression when IL levels are low. Selected-reaction monitoring mass spectrometry analysis revealed that at high IL concentrations EilA protein levels were significantly elevated under the control of PydfA' and PmarR' in comparison to the other promoters. Further, in a pooled culture competition designed to determine fitness, the strain containing pPmarR'-eilA outcompeted strains with other promoter constructs, most significantly at IL concentrations above 150 mM. These results indicate that native promoters such as PmarR' can provide effective systems for regulating the expression of heterologous genes in host engineering and simplify the development of industrially useful strains.

  19. Correction of murine hemoglobinopathies by prenatal tolerance induction and postnatal nonmyeloablative allogeneic BM transplants.

    Science.gov (United States)

    Peranteau, William H; Hayashi, Satoshi; Abdulmalik, Osheiza; Chen, Qiukan; Merchant, Aziz; Asakura, Toshio; Flake, Alan W

    2015-09-03

    Sickle cell disease (SCD) and thalassemias (Thal) are common congenital disorders, which can be diagnosed early in gestation and result in significant morbidity and mortality. Hematopoietic stem cell transplantation, the only curative therapy for SCD and Thal, is limited by the absence of matched donors and treatment-related toxicities. In utero hematopoietic stem cell transplantation (IUHCT) is a novel nonmyeloablative transplant approach that takes advantage of the immunologic immaturity and normal developmental properties of the fetus to achieve mixed allogeneic chimerism and donor-specific tolerance (DST). We hypothesized that a combined strategy of IUHCT to induce DST, followed by postnatal nonmyeloablative same donor "booster" bone marrow (BM) transplants in murine models of SCD and Thal would result in high levels of allogeneic engraftment and donor hemoglobin (Hb) expression with subsequent phenotypic correction of SCD and Thal. Our results show that: (1) IUHCT is associated with DST and low levels of allogeneic engraftment in the murine SCD and Thal models; (2) low-level chimerism following IUHCT can be enhanced to high-level chimerism and near complete Hb replacement with normal donor Hb with this postnatal "boosting" strategy; and (3) high-level chimerism following IUHCT and postnatal "boosting" results in phenotypic correction in the murine Thal and SCD models. This study supports the potential of IUHCT, combined with a postnatal nonmyelablative "boosting" strategy, to cure Thal and SCD without the toxic conditioning currently required for postnatal transplant regimens while expanding the eligible transplant patient population due to the lack of a restricted donor pool.

  20. Experimental Study on Induction of Tolerance to Experimental Autoimmune Myasthenia Gravis by Immature Dendritic Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the effect of immature dendritic cells (iDCs) on experimental autoimmune myasthenia gravis (MG), iDCs were generated in low dose of GM-CSF, and then they were pulsed with acetylcholine receptor (AchR) and transferred to allogeneic rats. After 3 weeks, all rats were immunized with AchR and complete Freund's adjuvant (CFA) and observed for the corresponding indices of MG for 7 weeks. Our results showed that compared with mature DCs (mDCs) generated at high dose of GM-CSF plus additional stimulation by lipopolysaccharide, iDCs expressed significantly lower levels of MHC-Ⅱ , CD80 and CD86, and their ability to uptake FITC-Dextran was stronger but the ability of stimulating proliferation of allogeneic T cells were weaker. Like controls,after immunization, all rats transferred with iDCs, mDCs and AchR-pulsed mDCs showed typical symptoms in 4 to 7 weeks. The amplitude of electromyogram wave dropped obviously, the level of serum AchRab increased and neuromuscular junction showed typical damage of MG. In contrast, no conspicuous changes were noted in rats transferred with AchR-pulsed iDCs. The results suggest that iDCs could be generated by inducing bone marrow precursors in low dose of GM-CSF, AchRpulsed iDCs could induce tolerance of EAMG. The dysfunction of DCs may play an important role in the initiation and maintenance of normal immune response in MG.

  1. Comparison of A1C to Oral Glucose Tolerance Test for the Diagnosis of Prediabetes in Overweight and Obese Youth.

    Science.gov (United States)

    Khokhar, Aditi; Naraparaju, Gayathri; Friedman, Miriam; Perez-Colon, Sheila; Umpaichitra, Vatcharapan; Chin, Vivian L

    2017-07-01

    IN BRIEF This study reports performance of A1C against the oral glucose tolerance test (OGTT) in predicting prediabetes among overweight and obese African-American and Caribbean children. A retrospective chart review was completed for 230 children. Receiver operating characteristic curves were generated to find the predictive performances of different tests against the OGTT. A1C alone is a poor discriminator of prediabetes in our study population, with low sensitivity (70%) and specificity (48.8%). BMI z score, A1C, and homeostatic model assessment of insulin resistance are significant predictors of prediabetes and, when taken together, provide better discrimination for prediabetes.

  2. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  3. A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

    Directory of Open Access Journals (Sweden)

    Katherine M Gaskell

    Full Text Available We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]. National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes.This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day.47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47. This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332. There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055].There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.

  4. Use of {sup 60}Co panoramic source in the induction of oral mucositis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Maira F.; Benetti, Carolina; Zezell, Denise M., E-mail: mairandrade@yahoo.com, E-mail: zezell@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Correa, Luciana, E-mail: lcorrea@usp.br [Universidade de Sao Paulo (FO/USP), Sao Paulo, SP (Brazil). Fac. de Odontologia

    2013-07-01

    Oral Mucositis is a well-known side effect of chemo-radiotherapy in cancer patients or transplant recipients that could induce hospitalization or impairs therapy in different levels of severity. This study is devoted to define the first steps in the research of low level laser treatments in oral mucositis, proposing a {sup 60}Co radiation to experimentally induce oral mucositis in rats using Panoramic gamma irradiator, simulating usual radiotherapy of head and neck cancer. Fifteen male Wistar rats, above 250g, were irradiated at Centro de Tecnologia das Radiacoes (IPEN - CNEN/SP) and divided in three experimental groups, with different single doses of radiation (30 Gy, 25 Gy and 20 Gy). The animals were observed for a 20 days period. Animals that received 30 Gy and 25 Gy developed greater severity of mucositis and premature euthanasia was performed in these groups on the 7th and 11th day after the irradiation, respectively. The 20 Gy group developed oral mucositis grading from moderated to severe between the days 7 and 11 after irradiation, with progressive body mass loss and decrease in the intake of food and water. These animals recovered from oral mucositis around the 18th day and clinical remission at the 20th day. The single dose of 20 Gy Gamma radiation proved to be efficient way for inducing oral mucositis in rats, allowing the establishment of an experimental model for oral mucositis in rats for future use on interventions of this serious aspect of radiation therapy, such as laser therapy using different wave lengths and power densities. (author)

  5. Insulin resistance and lipid profile during an oral glucose tolerance test in women with and without gestational diabetes mellitus.

    Science.gov (United States)

    Liang, Zx; Wu, Y; Zhu, Xy; Fang, Q; Chen, Dq

    2016-01-01

    We aimed to compare changes in insulin levels during an oral glucose tolerance test (OGTT) between women with normal glucose tolerance (NGT) during pregnancy and those with gestational diabetes mellitus (GDM). Overall, 105 pregnant women between 24 and 28 weeks' gestation, 50 with NGT and 55 with GDM according to NDDG standard, were enrolled into the study. The levels of fasting blood glucose, insulin, triglyceride (TG) and total cholesterol (TC) and the insulin levels, blood glucose levels at 1, 2 and 3 hours post oral glucose administration during an OGTT (5.8, 10.6, 9.2 and 8.1 mmol/L, respectively) were measured. Then, insulin resistance (IR) index was calculated. There was no significant difference in fasting, 3-h insulin levels and 3-h blood glucose levels between those with NGT and those with GDM (P > 0.05). However, 1-h and 2-h insulin levels, fasting and 1-h and 2-h blood glucose levels in women with GDM were significantly higher than those in the NGT group (P women with GDM was significantly lower than that observed in those with NGT. Reducing IR and blood lipids in women with GDM could potentially improve maternal and foetal outcomes.

  6. Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy

    National Research Council Canada - National Science Library

    Kim, Dong Wook; Gu, Nami; Jang, In‐Jin; Chu, Kon; Yu, Kyung‐Sang; Cho, Joo‐Youn; Yoon, Seo Hyun; Kim, Hwa Suk; Oh, Jeeyoung; Lee, Sang Kun

    2012-01-01

    The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients...

  7. Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2014-04-18

    Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

  8. A comparison of the efficacy and tolerability of oxcarbazepine oral suspension between infants and children with epilepsy: a retrospective chart review at a single medical center in Taiwan.

    Science.gov (United States)

    Wei, Shu-Hao; Liu, Cheng-Chao; Fan, Pi-Chuan

    2014-02-01

    Few clinical studies have assessed the efficacy and safety of oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly in infants. The aim of this study was to investigate and compare the efficacy, tolerability, and side effects of OXC oral suspension in Taiwanese infants and children with various types of epilepsy. A retrospective review of the efficacy, tolerability, and side effects of OXC oral suspension in a tertiary medical center in Taiwan was conducted and included children (1-9 years old) and infants (epilepsy, which was classified into idiopathic partial, symptomatic partial, or multifocal subtypes. The OXC oral suspension (Trileptal(®); Novartis) was given in a gradual dose titration, from an initial 7.5 mg/kg/day to 30 mg/kg/day within 1 month in all cases. A total of 20 infants and 38 children were identified. There were no statistically significant differences between the children and infants in efficacy (75 vs. 82 %, p = 0.734) and adverse effects (30 vs. 21 %, p = 0.525) after OXC oral suspension treatment. The efficacy was significantly correlated with the epilepsy subtype (p epilepsy responded better to OXC oral suspension than those with multifocal epilepsy. OXC oral suspension is effective and well tolerated in both infants and children with partial epilepsy in Taiwan. Treatment efficacy was related to epilepsy subtype and number of combined AEDs before OXC treatment. Monotherapy had an excellent therapeutic response in partial epilepsy but not in multifocal epilepsy.

  9. Induction of apoptosis by grape seed extract (Vitis vinifera) in oral squamous cell carcinoma.

    Science.gov (United States)

    Aghbali, Amirala; Hosseini, Sepideh Vosough; Delazar, Abbas; Gharavi, Nader Kalbasi; Shahneh, Fatemeh Zare; Orangi, Mona; Bandehagh, Ali; Baradaran, Behzad

    2013-08-01

    Development of novel therapeutic modalities is crucial for the treatment of oral squamous cell carcinoma (OSCC). Recent scientific studies have been focused on herbal medicines as potent anti-cancer drug candidates. This study is the first to investigate the cytotoxic effects and the mechanism of cell death induced by grape seed extract (GSE) in oral squamous cell carcinoma (KB cells). MTT (3-(4,5-dimetylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) and trypan blue assays were performed in KB cells as well as human umbilical vein endothelial cells (HUVEC) were used to analyze the cytotoxic activity of GSE. Furthermore, the apoptosis-inducing action of the extract was determined by TUNEL, DNA fragmentation and cell death analysis. Statistical significance was determined by analysis of variance (ANOVA), followed by Duncan's test at a significance level of P≤0.05. The results showed apoptotic potential of GSE, confirmed by significant inhibition of cell growth and viability in a dose- and time- dependent manner without inducing damage to non-cancerous cell line HUVEC. The results of this study suggest that this plant contains potential bioactive compound(s) for the treatment of oral squamous cell carcinoma.

  10. Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity.

    Science.gov (United States)

    Nash, A A; Gell, P G; Wildy, P

    1981-01-01

    Unresponsiveness to delayed type hypersensitivity was induced in mice following an intravenous injection of herpes simplex virus. The principal tolerogens used were thymidine kinase-deficient virus mutants which grow poorly in vivo; u.v.-inactivated and to a lesser extent formalin-inactivated virus were also tolerogenic. The tolerance induced was specific for the virus type. Despite the tolerance to delayed hypersensitivity, anti-viral immunity is present as determined by the rapid inactivation of infectious virus. The mechanism of tolerance to herpes virus and the importance of these observations for the pathogenesis of viral disease is discussed. PMID:7251047

  11. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...

  12. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1

    Directory of Open Access Journals (Sweden)

    Oertel Katrin

    2012-10-01

    Full Text Available Abstract Background Induction chemotherapy (ICT with docetaxel, cisplatin and fluorouracil (TPF followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. Methods Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0 and 30 mg/m2 (DL −1, plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. Results Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50% showed complete pathologic regression. Conclusions A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. Trial registration number NCT01108042 (ClinicalTrials.gov Identifier

  13. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Dominique N Price

    2016-05-01

    Full Text Available Bacille Calmette-Guérin (BCG is currently the only approved vaccine against tuberculosis (TB and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium, a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.

  14. Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

    Science.gov (United States)

    Price, Dominique N; Kusewitt, Donna F; Lino, Christopher A; McBride, Amber A; Muttil, Pavan

    2016-05-01

    Bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB) and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM) found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium), a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.

  15. Role of sodium silicate in induction of scleroderma-related autoantibodies in brown Norway rats through oral and subcutaneous administration.

    Science.gov (United States)

    Al-Mogairen, Sultan M

    2011-05-01

    Silica hazard is a growing occupational problem and has been reported to be associated with scleroderma via case reports and occupational studies. The aim of this study is to demonstrate whether oral or subcutaneous silicate exposure can induce an autoimmunity and scleroderma susceptibility in immunosensitive rats. Sodium silicate in a dose of 3 mg in 0.2 ml NS was administered through oral and subcutaneous routes to 20 brown Norway rats. Autoantibodies including ANA, anti-RNP, anti-SCL70 and anti-centromere were measured and compared with pre- and post-challenge serum samples. Serum ANA and anti-RNP were high in significant number of rats (P < 0.05) of only the subcutaneous silicate group. There is an increase in the number of positive readings of autoantibodies at 14th week in comparison with the number of positive readings of autoantibodies at 7th week but P values were not significant. It may be concluded that silicate might induce autoimmunity and scleroderma and it seems to be that the longer the duration of exposure the greater the risk. This is probably the first experimental animal study demonstrating the induction of scleroderma-related autoantibodies after challenge with silicate.

  16. DEHYDROEPIANDROSTERONE AND ORAL GLUCOSE TOLERANCE TEST IN YOUNG WOMEN: IS IT RELATED TO EACH OTHER?

    Directory of Open Access Journals (Sweden)

    A.M AMINI

    2001-09-01

    Full Text Available Introduction. In this study we wanted to compare the means of area under the curve (AVC of glucose tolerance test in young women depending on dehydroepiandrosteron (DHEA levels. Methods. Selected subjects were examined for DHEA and glucose tolerance test. At first, they were divided into two groups (under the mean of DHEA vs above the mean of DHEA and then into three groups (under the mean-SD, between the mean±SD, above the mean + SD. 37 young women with no abnormality whose 8MI was below 30 Kg/m2 they were refered to research center of endocrinology and metabolism of IUMSHS. Results. The mean of DHEA was 2895±1113 ng/ml. The mean of AUC was 745±104.7 mmol/l/min in women under the mean of DHEA and 670±51.9 mmol/l/min in women above the mean of DHEA (P < 0.05. In comparison of women based on mean±SD, the AVe was 786±88.3, 691. 7 ± 77.5 and 670.8±92.5 mmol/l/min, respectively. Results showed a significant decrease of AVC in women above the mean+ SO of DHEA (P < 0.05. Discussion. This study suggests that in young healthy women DHEA can increase the glucose tolerance.

  17. Prevention of Tracheal High-Dose Tolerance Induction by Granulocyte-Macrophage Colony Stimulating Factor- Dependent Restoration of Antigen-Presenting Cell Function

    Directory of Open Access Journals (Sweden)

    Kanna Haneda

    2000-01-01

    Full Text Available The intrusion of airborne allergens into airways elicits eosinophilic inflammation, as represented by bronchial asthma. It has been shown that excessive amounts of allergen in murine trachea lead to an unexpected evasion of deleterious eosinophilic inflammation by inducing T cell tolerance. In the present study, the mechanisms of tracheal high-dose tolerance are examined with regard to accessory cell functions and the effects of pro-inflammatory cytokines on tolerance. Antigen-induced tracheal eosinophilia was suppressed on instillation of high doses of antigen into the trachea, while concurrent instillation of granulocyte-macrophage colony stimulating factor (GM-CSF with the antigen restored the diminished responses. The restoration of eosinophilic infiltration by GM-CSF occurred in parallel with an increase in interleukin (IL-4 production by CD4+ T cells from the mediastinal lymph nodes. This was found to reflect the empowerment of antigen-presenting cells by GM-CSF, because the impaired ability of Ia+ cells from the tolerant mice to stimulate IL-4-producing T cells is restored by GM-CSF administration. The prevention of tolerance by up-regulating accessory cell functions is a feature unique to GM-CSF, because another pro-inflammatory cytokine, IL-iβ, failed to empower antigen-presenting cells. Thus, besides the induction of transforming growth factor-β-secreting CD4+ T cells, high-dose tolerance in the trachea includes an impairment of the accessory cell functions that support IL-4 production from T cells, which was reversed by GM-CSF. This report is the first demonstration that GM-CSF breaks the T cell tolerance of IL-4-producing T helper cells.

  18. Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?

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    V Noronha

    2015-01-01

    Full Text Available Background: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. Methods: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs between regimens. Results: Two hundred and forty-five patients were identified. The median age was 45 years (24–70 years, 208 (84.9% were male patients, and 154 patients (62.9% had primary in the Buccal mucosa. The regimens received were TPF 22 (9%, docetaxel + cisplatin 97 (39.6%, paclitaxel + cisplatin 89 (36.3%, docetaxel + carboplatin 16 (6.5% and paclitaxel + carboplatin 21 (8.6%. The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%, 56 (22.9%, 145 (59.2% and 40 (16.3%. The 3 drugs regimen (TPF had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004. Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094. Conclusions: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.

  19. Contributions of apoplasmic cadmium accumulation, antioxidative enzymes and induction of phytochelatins in cadmium tolerance of the cadmium-accumulating cultivar of black oat (Avena strigosa Schreb.).

    Science.gov (United States)

    Uraguchi, Shimpei; Kiyono, Masako; Sakamoto, Takuya; Watanabe, Izumi; Kuno, Katsuji

    2009-07-01

    The contributions of cadmium (Cd) accumulation in cell walls, antioxidative enzymes and induction of phytochelatins (PCs) to Cd tolerance were investigated in two distinctive genotypes of black oat (Avena strigosa Schreb.). One cultivar of black oat 'New oat' accumulated Cd in the leaves at the highest concentration compared to another black oat cultivar 'Soil saver' and other major graminaceous crops. The shoot:root Cd ratio also demonstrated that 'New oat' was the high Cd-accumulating cultivar, whereas 'Soil saver' was the low Cd-accumulating cultivar. Varied levels of Cd exposure demonstrated the strong Cd tolerance of 'New oat'. By contrast, low Cd-accumulating cultivar 'Soil saver' suffered Cd toxicity such as growth defects and increased lipid peroxidation, even though it accumulated less Cd in shoots than 'New oat'. Higher activities of ascorbate peroxidase (EC 1.11.1.11) and superoxide dismutase (EC 1. 15. 1. 1) were observed in the leaves of 'New oat' than in 'Soil saver'. No advantage of 'New oat' in PCs induction was observed in comparison to Cd-sensitive cultivar 'Soil saver', although Cd exposure increased the concentration of total PCs in both cultivars. Higher and increased Cd accumulation in cell wall fraction was observed in shoots of 'New oat'. On the other hand, in 'Soil saver', apoplasmic Cd accumulation showed saturation under higher Cd exposure. Overall, the present results suggest that cell wall Cd accumulation and antioxidative activities function in the tolerance against Cd stress possibly in combination with vacuolar Cd compartmentation.

  20. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents.

    Science.gov (United States)

    Derosa, Giuseppe

    2010-10-22

    Diabetes mellitus is a debilitating disease that is estimated to affect 366 million people by the year 2030. Type 2 diabetes mellitus (T2DM) is characterized by a progressive decline in pancreatic β-cell function and increased insulin resistance, and accounts for approximately 90% of people with diabetes. Oral antihyperglycaemic agents are extensively used in the treatment of T2DM. Thiazolidinediones are insulin sensitizers developed specifically for T2DM, which act via activation of peroxisome proliferator-activated receptors (PPARs). Pioglitazone is a thiazolidinedione that displays high affinity for PPARγ(1) and PPARγ(2), which are predominately expressed in adipose tissue. This review examines the published literature comparing the efficacy and tolerability of pioglitazone with other oral antihyperglycaemic agents in the treatment of patients with T2DM. Glycosylated haemoglobin, fasting glucose, insulin parameters and β-cell function are all improved with pioglitazone treatment, with efficacy similar to third-generation sulfonylureas, metformin and dipeptidyl peptidase-4 inhibitors. Pioglitazone reduces vascular risk and inflammatory markers, and improves carotid intima media thickness independent of its glycaemic effect. When compared with rosiglitazone, pioglitazone is associated with a reduction in the risk of hospitalization for acute myocardial infarction. Blood pressure is reduced and lipid profiles are favourably improved with pioglitazone; however, an increased risk for the development/exacerbation of heart failure, which is related to the increased incidence of oedema due to fluid retention, and fractures remain a concern. A low incidence of hypoglycaemia is observed with pioglitazone, especially compared with sulfonylureas. In conclusion, pioglitazone is an effective oral antihyperglycaemic agent with additional cardiovascular and lipid benefits that allows for the successful management of patients with T2DM.

  1. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

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    Sophie R Sayers

    Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

  2. Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation.

    Science.gov (United States)

    Horkheimer, Ian; Quigley, Michael; Zhu, Jiangao; Huang, Xiaopei; Chao, Nelson J; Yang, Yiping

    2009-05-21

    Tumor-specific T-cell tolerance represents one major mechanism of tumor-induced immune evasion. Myeloablative chemotherapy with stem cell transplantation may offer the best chance of achieving a state of minimal residual disease and, thus, minimize tumor-induced immune evasion. However, studies have shown that tumor-specific T-cell tolerance persists after transplantation. Here, we showed that CD4(+)CD25(+) regulatory T (T(Reg)) cells play a critical role in tumor-specific CD8(+) T-cell tolerance after transplantation. Removal of T(Reg) cells from the donor lymphocyte graft did not overcome this tolerance because of rapid conversion of donor CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) T(Reg) cells in recipients after transplantation, and depletion of T(Reg) cells in recipients was necessary for the reversal of tumor-specific tolerance. These results suggest that strategies capable of overcoming T-cell tolerance in recipients are required to promote antitumor immunity after transplantation. Toward this goal, we showed that dendritic cell (DC) vaccines coadministered with the TLR9 ligand, CpG could effectively overcome tumor-specific tolerance, leading to significant prolongation of tumor-free survival after transplantation. We further showed that CpG-induced type I interferon was critical for the reversal of tumor-specific tolerance in vivo. Collectively, these results may suggest effective immunotherapeutic strategies for treating cancer after stem cell transplantation.

  3. The SomnuSeal Oral Mask Is Reasonably Tolerated by Otherwise CPAP Noncompliant Patients with OSA

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    N. Katz

    2013-01-01

    Full Text Available Compliance with CPAP is the major limiting factor in treating patients with OSA. The novel SomnuSeal mask is an oral self-adaptable mask located between the teeth and the lips ensuring that there are no air leaks or skin abrasions. Fifty patients with AHI>20, who failed previous CPAP trials, were asked to sleep with the mask for one month. In all patients, the mask was connected to an AutoPAP machine with a heated humidifier. Efficacy, convenience, and compliance (average usage for 4 or more hours per night were monitored. Fifty patients (41 m and 9 f, mean age 57±12 years, BMI 33.6±4.9 kg/m2, and AHI 47±23/h participated. Eleven were classified as compliant (average mask usage of 26 nights, 4.7 hours per night, five were only partially compliant (average usage of 13 nights, 2.9 hours per night, and 34 could not comply with it. In all patients who slept with it, the efficacy (assessed by residual AHI derived from the CPAP device was good with an AHI of less than 8/hour. Interestingly, the required optimal pressure decreased from an average of 9.3 cmH2O to 4.6 cmH2O. The SomnuSeal oral interface is effective and may result in converting noncompliant untreated patients with OSA into well-treated ones.

  4. Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non-clinical safety testing after oral (gavage) dosing.

    Science.gov (United States)

    Elander, Mikael; Boll, Jette B; Hojman, Anne S; Rasmussen, Allan D

    2016-11-01

    The selection of a vehicle for oral formulations of compounds to be used in non-clinical safety studies is a challenge for poorly soluble compounds. Typically a compromise between solubility and tolerability has to be reached. Vehicle tolerability data are not readily available for a number of vehicles, and a series of oral tolerability studies were, therefore, conducted with Gelucire and Gelucire:PEG400 formulations in rats, dogs and minipigs in order to determine tolerable daily dose volumes in these species. Gelucire and Gelucire:PEG400 formulations were assessed in studies for up to 5 days in minipigs, 7 days in rats and up to 39 weeks in dogs. Gastrointestinal side effects in terms of soft and/or liquid faeces were noted in all species, but the sensitivity to these effects differed between species with the dog being the most sensitive. It was concluded that Gelucire:PEG400 (90:10) was tolerated in Beagle dogs when administered at 1 ml kg(-1) once daily for 39 weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5 ml kg(-1) for 5 days. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model.

    Science.gov (United States)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9-18 fold) of induction in the microarray data, and its early induction was observed in a 2h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  6. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  7. Characterization of Electronic Cigarette Aerosol and Its Induction of Oxidative Stress Response in Oral Keratinocytes.

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    Eoon Hye Ji

    Full Text Available In this study, we have generated and characterized Electronic Cigarette (EC aerosols using a combination of advanced technologies. In the gas phase, the particle number concentration (PNC of EC aerosols was found to be positively correlated with puff duration whereas the PNC and size distribution may vary with different flavors and nicotine strength. In the liquid phase (water or cell culture media, the size of EC nanoparticles appeared to be significantly larger than those in the gas phase, which might be due to aggregation of nanoparticles in the liquid phase. By using in vitro high-throughput cytotoxicity assays, we have demonstrated that EC aerosols significantly decrease intracellular levels of glutathione in NHOKs in a dose-dependent fashion resulting in cytotoxicity. These findings suggest that EC aerosols cause cytotoxicity to oral epithelial cells in vitro, and the underlying molecular mechanisms may be or at least partially due to oxidative stress induced by toxic substances (e.g., nanoparticles and chemicals present in EC aerosols.

  8. Induction of prostaglandin E(2) and interleukin-6 in gingival fibroblasts by oral biofilms.

    Science.gov (United States)

    Belibasakis, Georgios N; Guggenheim, Bernhard

    2011-12-01

    Polymicrobial oral biofilms attaching on tooth surfaces can trigger inflammatory responses by the neighbouring tooth-supporting periodontal tissues. An excessive inflammatory response can cause destruction of the periodontal tissues, including the alveolar bone, thus resulting in periodontitis. Mediators of inflammation, such as prostaglandin E(2) (PGE(2) ) and interleukin-6, are primary regulators of alveolar bone destruction in periodontitis. The present study aimed to comparatively investigate the effects of in vitro supragingival and subgingival biofilms, on the regulation of PGE(2) and interleukin-6 in human gingival fibroblasts. The cells were challenged with culture supernatants of the two biofilms for 6 h. Cyclo-oxygenase (COX)-2, an enzyme responsible for the conversion of PGE(2) , and interleukin-6 gene expression were analysed by quantitative real-time PCR. The production of PGE(2) and interleukin-6 by the cells was analysed by ELISA. While the supragingival biofilm did not induce significant changes, the subgingival biofilm caused an 8.6- and 2.9-fold enhancement of COX-2 and interleukin-6 gene expression, respectively, and a 72.5- and 1.5-fold enhancement of PGE(2) and interleukin-6 production, respectively. In conclusion, subgingival biofilms are potent inducers of PGE(2) in gingival fibroblasts, providing further mechanistic insights into the association of subgingival biofilms with bone resorption periodontitis.

  9. Induction of Mitochondrial Dysfunction and Oxidative Stress in Leishmania donovani by Orally Active Clerodane Diterpene

    Science.gov (United States)

    Kathuria, Manoj; Bhattacharjee, Arindam; Sashidhara, Koneni V.; Singh, Suriya Pratap

    2014-01-01

    This study was performed to investigate the mechanistic aspects of cell death induced by a clerodane diterpene (K-09) in Leishmania donovani promastigotes that was previously demonstrated to be safe and orally active against visceral leishmaniasis (VL). K-09 caused depolarization of the mitochondrion and the generation of reactive oxygen species, triggering an apoptotic response in L. donovani promastigotes. Mitochondrial dysfunction subsequently resulted in the release of cytochrome c into the cytosol, impairing ATP production. Oxidative stress caused the depletion of reduced glutathione, while pretreatment with antioxidant N-acetyl cysteine (NAC) was able to abrogate oxidative stress. However, NAC failed to restore the mitochondrial membrane potential or intracellular calcium homeostasis after K-09 treatment, suggesting that the generation of oxidative stress is a downstream event relative to the other events. Caspase-3/-7-like protease activity and genomic DNA fragmentation were observed. Electron microscopy studies revealed gross morphological alterations typical of apoptosis, including severe mitochondrial damage, pyknosis of the nucleus, structural disruption of the mitochondrion-kinetoplast complex, flagellar pocket alterations, and the displacement of organelles. Moreover, an increased number of lipid droplets was detected after K-09 treatment, which is suggestive of altered lipid metabolism. Our results indicate that K-09 induces mitochondrial dysfunction and oxidative stress-mediated apoptotic cell death in L. donovani promastigotes, sharing many features with metazoan apoptosis. These mechanistic insights provide a basis for further investigation toward the development of K-09 as a potential drug candidate for VL. PMID:25070112

  10. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    Science.gov (United States)

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation.

  11. The assessment of tolerability of prolonged oral eugenol administration in rats

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    Jezdimirović Milanka

    2012-01-01

    Full Text Available The potential toxicity and general tolerability of eugenol following two-week or four-week continuous p.o. administration to rats has been investigated. An experiment was performed on 72 male rats of the Wistar strain. Four groups of rats were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg, 200 mg/kg and 400 mg/kg bm/day, the fifth group was administered vehicle (0.5 % methylcellulose, propylene glycol and water, and the sixth group comprised absolutely untreated controls. The corresponding doses of eugenol and vehicle were applied using a gastric probe in a volume of 1 ml/100 g body mass. The general tolerability of eugenol was evaluated on the basis of the daily intake of water and food, body mass, general health condition, behaviour, and lethality in the course of the experiment. In the investigated doses, eugenol applied p.o. in the course of two or four weeks does not influence significantly the intake of food, water, or body mass of rats. The dose of 400 mg/kg/day produced undesired reactions (agitation and hyperesthesia that were first observed on day 21 and lasted until the end of the experiment. Low subacute toxicity of eugenol was established following p.o. administration to rats. Eugenol in doses of 200 and 400 mg/kg tm/day has a low toxic potential and is safe for administration to this animal species. [Projekat Ministarstva nauke Republike Srbije, br. 46009

  12. Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol.

    Science.gov (United States)

    Stampf, J L; Benezra, C; Byers, V; Castagnoli, N

    1986-05-01

    Previous studies have established that epicutaneous application of 5-methyl-3-n-pentadecylcatechol (5-Me-PDC), a synthetic analog of a poison ivy urushiol component, leads to immune tolerance to 3-n-pentadecylcatechol (PDC) in mice. The induction of tolerance by 5-Me-PDC may be mediated by a protein conjugate formed via selective reaction of thiol nucleophiles present on the carrier macromolecule with the corresponding o-quinone derived from the parent catechol. In order to examine further the tolerogenic properties of 5-Me-PDC, we have extended our studies to the guinea pig, the generally accepted experimental species for the study of contact allergy. The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog. Furthermore, we were able to show that the treated animals remained tolerant for at least 6 weeks, a period of time comparable to that observed following the intravenous administration of the O,O-bis-acetyl derivative of PDC. The data point to the possibility of developing a therapeutically effective topical tolerogen for poison ivy contact dermatitis.

  13. Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Hung, Cheng-Han; Cheng, Shi-Yann; Chan, Tzu-Min; Lee, Maw-Rong

    2015-09-01

    Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (μElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using μElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction.

  14. 78 FR 57868 - Prospective Grant of Exclusive Patent License: Oral Treatment of Hemophilia

    Science.gov (United States)

    2013-09-20

    ... Treatment of Hemophilia AGENCY: National Institutes of Health, HHS. ACTION: Notice. SUMMARY: This is notice..., ``Oral Treatment of Hemophilia'' and ``Induction of Tolerance by Oral administration of Factor VIII and Treatment of Hemophilia''. The patent rights in these inventions have been assigned to or exclusively...

  15. Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin.

    Science.gov (United States)

    Mizoguchi, Yoko; Furue, Aya; Kagawa, Reiko; Chijimatsu, Ikue; Tomioka, Keita; Shimomura, Maiko; Imanaka, Yusuke; Nishimura, Shiho; Saito, Satoshi; Miki, Mizuka; Ono, Atsushi; Konishi, Nakao; Kawaguchi, Hiroshi; Kobayashi, Masao

    2016-04-01

    The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors.

  16. Effect of cyanocobalamin (vitamin B12) in the induction and expression of morphine tolerance and dependence in mice.

    Science.gov (United States)

    Ghazanfari, S; Imenshahidi, M; Etemad, L; Moshiri, M; Hosseinzadeh, H

    2014-03-01

    The antinociceptive effect of cyanocobalamin (Vit B12) has been reported in animal models and human studies. Our previous study showed the effect of Vit B12 on morphine tolerance. The dependence and tolerance were induced in male mice using subcutaneous morphine injections, 3 times a day (50, 50 and 75 mg/kg/day) for 3 days. Mice also received Vit B12 (100, 250 and 500 µg/kg), clonidine, memantine and saline intraperitoneally before morphine administration. On fourth day mice received only 7 mg /kg morphine just before tail-flick test. To determine the expression of morphine dependence and tolerance, all compounds were injected once intraperitoneally on the day of experiment. The tolerance was evaluated by the tail-flick test. The effect of Vit B12 and other agents on dependence were evaluated by counting the number of jumps (induced by naloxone 5 mg/kg). Co-administration of Vit B12 (100-500 µg/kg) and morphine in 3 days reduced the development of tolerance to morphine analgesic effect (8.2±0.5 and 7.83±0.5 s. vs. normal saline, 3.57±0.3 s). Repeated administration of Vit B12, also, diminished the reduced naloxane withdrawal signs of naloxone withdrawal test (100-500 µg/kg: 5±1.9 and 1.2±0.8 jumps vs. normal saline 72.6±12.2). However, Vit B12 had no effect on the expression of morphine tolerance and physical dependence. It is concluded that co-administration of Vit B12 and morphine could reduce tolerance to analgesic effect of morphine chronic administration and also reduce its withdrawal symptoms. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Suppressive therapy versus episodic therapy with oral valacyclovir for recurrent herpes labialis: efficacy and tolerability in an open-label, crossover study.

    Science.gov (United States)

    Gilbert, Stanley C

    2007-04-01

    Oral valacyclovir's efficacy and tolerability as suppressive therapy versus episodic therapy were compared for recurrent herpes labialis (RHL). Subjects with a history of at least 3 RHL episodes in the past year were randomized to receive 6 months of oral valacyclovir episodic therapy at the first sign of prodrome (two 2-g doses separated by 12 hours) and 6 months of oral valacyclovir suppressive therapy (1 g once daily) for 6 months in open-label, crossover fashion. The mean +/- SE number of recurrences per 120 days of follow-up (primary endpoint) was lower with suppressive therapy (0.30 +/- 0.41) than episodic therapy (0.71 +/- 0.79) (P 180 days) for suppressive therapy (P = 0.021). Data for secondary efficacy endpoints (pain severity score, mean duration of recurrences, maximal total lesion area) showed approximately a 30% to 50% reduction in mean values with suppressive therapy compared with episodic therapy, but results were statistically significantly different between the regimens for pain severity only. The percentage of subjects with at least one adverse event over 6 months of treatment that was considered to be drug related was 3% with suppressive therapy and 6% with episodic therapy. Suppressive therapy with oral valacyclovir was more effective than episodic therapy with oral valacyclovir in reducing the frequency of recurrences of herpes labialis and prolonging the time to first recurrence and was also similarly well-tolerated.

  18. Investigation of the tolerability of oral stevioside in Brazilian hyperlipidemic patients

    Directory of Open Access Journals (Sweden)

    Gisleine Elisa Cavalcante da Silva

    2006-07-01

    Full Text Available The tolerability of stevioside (2.75 mg/kg/day obtained from leaves of Stevia rebaudiana (Bert Bertoni (Compositae was investigated in hyperlipidemic patients. For this purpose a placebo controlled double blind study was performed. The patients were randomized in two groups: the first group received capsules containing placebo and the second group received capsules containing stevioside (50 mg during 90 days. All capsules were ingested twice daily, i.e., 2 capsules before lunch and 2 capsules before dinner. After the selection of the patients and each 30 days body mass index and laboratory tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, total cholesterol, high density lipoprotein, low density lipoprotein, very low density lipoprotein, triglycerides and glucose were performed. Stevioside did not show any clinical relevant modification in all parameters investigated. Moreover the patients did not report severe adverse effect. Thus, we can concluded that stevioside, at least in the doses employed in this study was safe.A tolerabilidade do esteviosideo (2.75 mg/kg/dia obtido a partir de folhas de Stevia rebaudiana (Bert Bertoni (Compositae foi investigada em pacientes hiperlipidêmicos. Para alcançar este objetivo realizamos estudo clínico do tipo duplo cego. Os pacientes foram randomizados em 2 grupos: o primeiro recebeu cápsulas contendo placebo e o segundo recebeu cápsulas contendo esteviosídeo (50 mg. Foram ingeridas duas cápsulas antes do almoço e duas cápsulas antes do jantar durante 90 dias. Após a seleção dos pacientes e a cada 30 dias o índice de massa corpórea e exames laboratoriais (alanina aminotransferase, aspartato aminotransferase, gama-glutamiltransferase, colesterol total, lipoproteína de alta densidade, lipoproteína de baixa densidade, lipoproteína de muito baixa densidade, trigliceridemia e glicemia foram realizados. O esteviosídeo não acarretou qualquer altera

  19. Hemolysis is a major cause of variability in insulin measurement during oral glucose tolerance test in children.

    Science.gov (United States)

    Bellomo, Giorgio; Sulas, Maria Giovanna; Mairate, Elisabetta; Bardone, Maria Beatrice; Rolla, Roberta

    2012-01-01

    The oral glucose tolerance test (OGTT) is widely employed to evaluate insulin resistance in children with growth hormone deficiency. Due to the difficulty in blood sampling, hemolysis is a frequent pre-analytic interference. The present study was performed to characterize the effects of hemolysis on insulin assays, in order to assess the need to generate automatic hemolysis reports and/or to reject hemolyzed samples. Insulin plasma levels were measured using a Siemens ADVIA Centaur on samples obtained from children with suspected GH deficiency at risk for insulin resistance during OGTT. The presence of hemolysis (with a concentration of free hemoglobin above 75 mg/dL) promotes a dose- and time-dependent decrease in immunoreactive insulin at any time-point evaluated during OGTT. As a consequence, the variability of insulin is particularly high (often exceeding 100% of the mean value) as compared to that of glucose. This variability is markedly reduced after removal of the hemolyzed samples. When hemolysis is not taken into account a misinterpretation of insulin secretion pattern can occur. It is therefore imperative to: (i) analyze blood samples immediately after sampling, (ii) reject samples with a concentration of free hemoglobin equal to or above 125 mg/dL and (iii) always report the possible interference.

  20. Stability evaluation of freeze-dried Lactobacillus paracasei subsp. tolerance and Lactobacillus delbrueckii subsp. bulgaricus in oral capsules.

    Science.gov (United States)

    Jalali, M; Abedi, D; Varshosaz, J; Najjarzadeh, M; Mirlohi, M; Tavakoli, N

    2012-01-01

    Freeze-drying is a common preservation technology in the pharmaceutical industry. Various studies have investigated the effect of different cryoprotectants on probiotics during freeze-drying. However, information on the effect of cryoprotectants on the stability of some Lactobacillus strains during freeze-drying seems scarce. Therefore, the aim of the present study was to establish production methods for preparation of oral capsule probiotics containing Lactobacillus paracasei subsp. tolerance and Lactobacillus delbrueckii subsp. Bulgaricus. It was also of interest to examine the effect of various formulations of cryoprotectant media containing skim milk, trehalose and sodium ascorbate on the survival rate of probiotic bacteria during freeze-drying at various storage temperatures. Without any cryoprotectant, few numbers of microorganisms survived. However, microorganisms tested maintained higher viability after freeze-drying in media containing at least one of the cryoprotectants. Use of skim milk in water resulted in an increased viability after lyophilization. Media with a combination of trehalose and skim milk maintained a higher percentage of live microorganisms, up to 82%. In general, bacteria retained a higher number of viable cells in capsules containing freeze-dried bacteria with sodium ascorbate after three months of storage. After this period, a marked decline was observed in all samples stored at 23°C compared to those stored at 4°C. The maximum survival rate (about 72-76%) was observed with media containing 6% skim milk, 8% trehalose and 4% sodium ascorbate.

  1. Effects of addition of ketamine, fentanyl and saline with Propofol induction on hemodynamics and laryngeal mask airway insertion conditions in oral clonidine premedicated children

    Directory of Open Access Journals (Sweden)

    Tanmoy Ghatak

    2012-01-01

    Full Text Available Background: The aim of this double-blind, prospective, randomized, controlled study was to compare the effect of addition of ketamine; fentanyl and saline with propofol anesthesia on hemodynamic profile and laryngeal mask airway (LMA insertion conditions in oral clonidine premedicated children. Methods: 180 children (age 2 - 10 years were at first given oral clonidine (4 μg/kg 90 minutes before operation, and then were randomly allocated to receive either ketamine 0.5 mg/kg (n=60, fentanyl 1 μg/kg (n=60 or 0.9% normal saline (n=60 before induction with propofol 3.0 mg/kg. Insertion of LMA was performed within 1 minute of injection of propofol. Heart rate and mean blood pressure were noted 1 min before induction (baseline, immediately after induction, before and after insertion of LMA for up to 3 min. Following LMA insertion, 6 subjective end points were noted-mouth opening, coughing, swallowing, patient′s movement, laryngospasm, and ease of an insertion. LMA insertion summed score was prepared depending upon these variables. Results: LMA insertion summed score was nearly similar in ketamine and fentanyl group, which were significantly better than saline group (P120 secs. was higher in fentanyl group compared to ketamine and saline group. Conclusion: Even in oral clonidine premedicated children, addition of ketamine with propofol provides hemodynamic stability and comparable conditions for LMA insertion like fentanyl propofol with significantly less prolonged apnea.

  2. Tolerance of CD8+ T cells developing in parent-->F1 chimeras prepared with supralethal irradiation: step-wise induction of tolerance in the intrathymic and extrathymic environments.

    Science.gov (United States)

    Kosaka, H; Sprent, J

    1993-02-01

    Tolerance of CD8+ cells was examined in parent-->F1 bone marrow chimeras (BMC) prepared with supralethal irradiation; host class I expression in the chimeras was limited to non-BM-derived cells. In terms of helper-independent proliferative responses in vitro and induction of graft-vs.-host disease on adoptive transfer, CD8+ cells from long-term chimeras showed profound tolerance to host antigens irrespective of whether the cells were prepared from the thymus or from spleen or lymph nodes. By limiting dilution analysis, cytotoxic T lymphocyte (CTL) precursors specific for host antigens were rare in the extrathymic lymphoid tissues. In the thymus, by contrast, host-specific CTL precursors were only slightly less frequent than in normal parental strain mice. These host-specific CD8+ cells survived when BMC thymocytes were transferred intravenously to a neutral environment, i.e., to donor strain mice. When transferred to further BMC hosts, however, most of the host-reactive cells disappeared. Collectively, the data suggest that tolerance of CD8+ cells in BMC hosts occurs in both the intrathymic and extrathymic environments. In the thymus, contact with host antigens on thymic epithelial cells deletes CD8+ cells controlling helper-independent proliferative responses and in vivo effector functions but spares typical helper-dependent CTL precursors. After export from the thymus, most of the CTL precursors are eliminated after contacting host antigens on stromal cells in the extrathymic environment.

  3. Induction and differential expression of beta-1,3-glucanase mRNAs in tolerant and susceptible Hevea clones in response to infection by Phytophthora meadii.

    Science.gov (United States)

    Thanseem, I; Joseph, A; Thulaseedharan, A

    2005-11-01

    Most cultivated rubber tree (Hevea brasiliensis Willd. ex A. Juss.) clones in India are susceptible to abnormal leaf fall disease (ALF), which is caused by various Phytophthora species and results in yield losses of up to 40%. Because the conventional breeding programs for this perennial tree crop are complex and time consuming, we attempted to find a molecular solution to increase the tolerance of rubber trees to ALF. The expression patterns of the gene coding for the pathogenesis-related beta-1,3-glucanase (beta-glu) enzyme in a tolerant (RRII 105) and a highly susceptible (RRIM 600) clone of rubber tree were examined, following infection with ALF-causing Phytophthora meadii McRae. Infected leaf samples were collected at different times after inoculation, and RNA was extracted and subjected to Northern blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). On hybridization with a 1.25 kb beta-glu probe, Northern blots showed a marked increase in beta-glu transcript levels in both clones 48 h after inoculation. However, compared with the susceptible RRIM 600 clone, the tolerant RRII 105 clone had a higher rate of increase and a more prolonged induction, with beta-glu transcript levels remaining high for 4 days after inoculation. In RRIM 600, the mRNA levels decreased significantly 48 h after inoculation. On re-hybridization with an 18S rRNA probe, uniform signals were detected in all the lanes, indicating that an equal amount of total RNA was present in all samples. Similar results were obtained in relative quantitative RT-PCR experiments with the housekeeping actin gene as an internal control. Thus, although induction of the beta-glu gene occurred in both tolerant and susceptible clones, the predominant difference between clones was in the intensity and duration of the response. The tolerance of clone RRII 105 may be associated with the prolonged expression of the gene following infection. The antifungal activity of these hydrolase

  4. Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials.

    Science.gov (United States)

    Lee, Deborah; Kalu, Uwa; Halford, Jonathan J; Biton, Victor; Cloyd, James; Klein, Pavel; Bekersky, Ihor; Peng, Guangbin; Dheerendra, Suresh; Tolbert, Dwain

    2015-06-01

    To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959). Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations. Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥ 5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received oral and IV carbamazepine. IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations. © 2015 Lundbeck LLC. Epilepsia published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

  5. Induction of salt tolerance and up-regulation of aquaporin genes in tropical corn by rhizobacterium Pantoea agglomerans.

    Science.gov (United States)

    Gond, S K; Torres, M S; Bergen, M S; Helsel, Z; White, J F

    2015-04-01

    Bacteria were isolated from surface disinfected seeds of eight modern corn types and an ancestor of corn, 'teosinte' and identified using 16S rDNA sequences. From each of the modern corn types we obtained Bacillus spp. (including, Bacillus amyloliquefaciens and Bacillus subtilis); while from teosinte we obtained only Pantoea agglomerans and Agrobacterium species. Of these bacteria, only P. agglomerans could actively grow under hypersaline conditions and increase salt tolerance of tropical corn seedlings. In laboratory and greenhouse experiments where plants were watered with a 0.2 mol l(-1) NaCl solution, P. agglomerans was found to enhance the capacity of tropical corn to grow compared to uninoculated controls. The total dry biomass was significantly higher in P. agglomerans-treated plants compared to controls under saline water. Gene expression analysis showed the up-regulation of the aquaporin gene family especially plasma membrane integral protein (ZmPIP) genes in P. agglomerans-treated plants. The plasma membrane integral protein type 2 (PIP2-1) gene in tropical corn seedlings was highly up-regulated by P. agglomerans treatment under salt stress conditions. Microscopic examination of P. agglomerans inoculated seedlings revealed that the bacterium colonized root meristems densely, and as roots developed, the bacterium became sparsely located in cell junctions. The enhancement of salt tolerance capacity in tropical corn, an important food crop, has the capacity to increase its cultivation area and yield in saline soils. The application of rhizobacteria to improve salt tolerance of tropical corn is ecofriendly and cost effective. We show that P. agglomerans isolated from teosinte (an ancestor of corn) induces salt tolerance in tropical corn and up-regulation of aquaporin genes. This study shows that microbes that increase salt tolerance may be used to enhance crop growth in saline soils. © 2014 The Society for Applied Microbiology.

  6. Absorption and tolerability of fentanyl buccal soluble film (FBSF in patients with cancer in the presence of oral mucositis

    Directory of Open Access Journals (Sweden)

    Finn AL

    2011-09-01

    Full Text Available Andrew L Finn1, WD Charlie Hill2, Ignacio Tagarro3, Larry N Gever41Product Development, BioDelivery Sciences International, Inc, Raleigh, NC, USA; 2Co-founding partner, InVisions Consultants, LLC, San Antonio, TX, USA; 3Marketing Centre CIP CNS, Meda Pharma S.A.U., Madrid, Spain; 4Medical Affairs, Meda Pharmaceuticals, Inc, Somerset, NJ, USAPurpose: Fentanyl buccal soluble film (FBSF consists of a small, bilayered, water-soluble polymer film that adheres to the buccal mucosa and rapidly delivers fentanyl into the systemic circulation. The purpose of this study was to evaluate the absorption of fentanyl from FBSF in patients with cancer, with and without grade 1 oral mucositis, and to assess the tolerability of FBSF in this patient population.Patients and methods: In an open-label, single-dose study, two groups of opioid-naive patients (ie, not receiving opioids on a regular basis with cancer received a 200 µg dose of FBSF. Patients in cohort I (n = 7 had grade 1 mucositis, and patients in cohort II (n = 7 were age- and gender-matched controls without mucositis. The FBSF dose was placed on the area of mucositis in cohort I and on a matching location in cohort II. Blood samples were collected up to 4 hours after administration, and safety assessments were made throughout the study.Results: Peak plasma concentration and area under the concentration–time curve from time 0 to 4 hours post-dose values of patients in the grade 1 mucositis cohort were lower than those observed in patients without mucositis. There was no application site irritation reported in any patient, regardless of mucositis status. Mild somnolence was reported by two patients with mucositis. There were no deaths or serious adverse events reported in this study.Conclusion: The results of this study indicate that application of FBSF to an area of grade 1 mucositis does not result in increased fentanyl exposure or irritation of the mucosa. The 200 µg dose of FBSF was well

  7. Role of cholecystokinin in anorexia induction following oral exposure to the 8-ketotrichothecenes deoxynivalenol, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, fusarenon X, and nivalenol.

    Science.gov (United States)

    Wu, Wenda; Zhou, Hui-Ren; He, Kaiyu; Pan, Xiao; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Zhang, Haibin; Pestka, James J

    2014-04-01

    Cereal grain contamination by trichothecene mycotoxins is known to negatively impact human and animal health with adverse effects on food intake and growth being of particular concern. The head blight fungus Fusarium graminearum elaborates five closely related 8-ketotrichothecene congeners: (1) deoxynivalenol (DON), (2) 3-acetyldeoxynivalenol (3-ADON), (3) 15-acetyldeoxynivalenol (15-ADON), (4) fusarenon X (FX), and (5) nivalenol (NIV). While anorexia induction in mice exposed intraperitoneally to DON has been linked to plasma elevation of the satiety hormones cholecystokinin (CCK) and peptide YY₃₋₃₆ (PYY₃₋₃₆), the effects of oral gavage of DON or of other 8-keotrichothecenes on release of these gut peptides have not been established. The purpose of this study was to (1) compare the anorectic responses to the aforementioned 8-ketotrichothecenes following oral gavage at a common dose (2.5 mg/kg bw) and (2) relate these effects to changes plasma CCK and PYY₃₋₃₆ concentrations. Elevation of plasma CCK markedly corresponded to anorexia induction by DON and all other 8-ketotrichothecenes tested. Furthermore, the CCK1 receptor antagonist SR 27897 and the CCK2 receptor antagonist L-365,260 dose-dependently attenuated both CCK- and DON-induced anorexia, which was consistent with this gut satiety hormone being an important mediator of 8-ketotrichothecene-induced food refusal. In contrast to CCK, PYY₃₋₃₆ was moderately elevated by oral gavage with DON and NIV but not by 3-ADON, 15-ADON, or FX. Taken together, the results suggest that CCK plays a major role in anorexia induction following oral exposure to 8-ketotrichothecenes, whereas PYY₃₋₃₆ might play a lesser, congener-dependent role in this response.

  8. Phase I study to determine the maximal tolerated dose and dose-limiting toxicities of orally administered idarubicin in dogs with lymphoma.

    Science.gov (United States)

    Vail, D M; Husbands, B D; Kamerling, S G; Simpson, H; Kurzman, I D; McDonnell, A

    2012-01-01

    Idarubicin, a PO bioavailable anthracycline antibiotic-class chemotherapeutic, could have substantial convenience advantages over currently available similar class agents in use that require IV delivery. The primary objective of this study was to determine the maximally tolerated dose (MTD), dose-limiting toxicities (DLTs), and basic pharmacokinetic parameters of oral idarubicin exposure in dogs with lymphoma after a single oral dose. A secondary objective was to document preliminary antitumor efficacy in an expanded treatment cohort using the established MTD. Client-owned dogs with measurable lymphoma. Dogs (n = 31) were enrolled in a prospective open label phase I study of oral idarubicin. By means of a 3 + 3 cohort design, dose escalations were made with 3 dogs per dose level, and the MTD was established based on the number of patients experiencing a DLT. Plasma concentrations of idarubicin and idarubicinol were determined by postdose sampling. Assessment of antitumor efficacy focused on evaluation of accessible, measurable lymph nodes and skin lesions by modified RECIST guidelines. The MTD in dogs > 15 kg body weight was 22 mg/m(2) . Adverse hematologic events (neutropenia and thrombocytopenia) were the predominant DLT and generally correlated with higher plasma concentrations of idarubicin and idarubicinol. PO administered idarubicin was generally well-tolerated and had preliminary antitumor activity in dogs with lymphoma. Furthermore, the potential clinical advantage of a safe and efficacious oral anthracycline alternative supports further investigations of this agent in repeated-dose, randomized clinical trials. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  9. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

    DEFF Research Database (Denmark)

    Steg, Ph Gabriel; Mehta, Shamir R; Jukema, J Wouter

    2011-01-01

    To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS)....

  10. Bacillus licheniformis SA03 Confers Increased Saline–Alkaline Tolerance in Chrysanthemum Plants by Induction of Abscisic Acid Accumulation

    Directory of Open Access Journals (Sweden)

    Cheng Zhou

    2017-06-01

    Full Text Available Soil saline-alkalization is a major abiotic stress that leads to low iron (Fe availability and high toxicity of sodium ions (Na+ for plants. It has recently been shown that plant growth promoting rhizobacteria (PGPR can enhance the ability of plants to tolerate multiple abiotic stresses such as drought, salinity, and nutrient deficiency. However, the possible involvement of PGPR in improving saline–alkaline tolerance of plants and the underlying mechanisms remain largely unknown. In this study, we investigated the effects of Bacillus licheniformis (strain SA03 on the growth of Chrysanthemum plants under saline–alkaline conditions. Our results revealed that inoculation with SA03 alleviated saline–alkaline stress in plants with increased survival rates, photosynthesis and biomass. The inoculated plants accumulated more Fe and lower Na+ concentrations under saline–alkaline stress compared with the non-inoculated plants. RNA-Sequencing analyses further revealed that SA03 significantly activated abiotic stress- and Fe acquisition-related pathways in the stress-treated plants. However, SA03 failed to increase saline–alkaline tolerance in plants when cellular abscisic acid (ABA and nitric oxide (NO synthesis were inhibited by treatment with fluridone (FLU and 2-(4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO, respectively. Importantly, we also found that NO acted downstream of SA03-induced ABA to activate a series of adaptive responses in host plants under saline–alkaline stress. These findings demonstrated the potential roles of B. licheniformis SA03 in enhancing saline–alkaline tolerance of plants and highlighted the intricate integration of microbial signaling in regulating cellular Fe and Na+ accumulation.

  11. Plasma total oxidant and antioxidant status after oral glucose tolerance and mixed meal tests in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Kucukaydın, Zehra; Duran, Cevdet; Basaran, Mustafa; Camlica, Fatos; Erdem, Sami Said; Basaran, Ahmet; Kutlu, Orkide; Burnik, Ferda Sevimli; Elmas, Halis; Gonen, Mustafa Sait

    2016-10-01

    Insulin resistance (IR) and increased oxidative stress (OS) are the characteristics of polycystic ovary syndrome (PCOS). In this study, we aimed to evaluate the effects of oral glucose tolerance (OGTT) and mixed meal tests (MMT) on plasma total oxidant (TOS) and total antioxidant status (TAS) in patients with PCOS and the relationship between these parameters and IR, calculated via homeostasis of model assessment-IR (HOMA-IR) and Matsuda's insulin sensitivity index (ISI) derived from OGTT and MMT. Twenty-two patients with PCOS, and age- and body mass index (BMI)-matched 20 women as controls were enrolled into the study. Five-hour OGTT and MMT were performed on different days, and before and after these tests, plasma TOS and TAS levels were investigated. IR was calculated with HOMA-IR and Matsuda's ISI. HOMA-IR levels were higher in patients with PCOS, compared to controls, while Matsuda's ISI derived from OGTT and MMT was higher in controls. Plasma TOS levels before OGTT and MMT were higher in patients with PCOS than controls, while TAS levels were similar. After OGTT, plasma TOS levels became decreased at 5th hour, when compared to baseline values in PCOS group. Likewise, the same decrement was found in controls, but the decrement was not significant. After OGTT and MMT at 5th hour, no changes were observed in TAS levels, compared to baseline. Matsuda's ISIs derived from OGTT and MMT can be used instead of each other, and interestingly, we found a decrease in TOS levels after OGTT in patients with PCOS.

  12. Higher incremental insulin area under the curve during oral glucose tolerance test predicts less food intake and weight gain.

    Science.gov (United States)

    He, J; Votruba, S; Venti, C; Krakoff, J

    2011-12-01

    To investigate the correlation of peripheral insulin concentrations with food intake and body weight. Cross sectional and longitudinal clinical study: we investigated the association of peripheral insulin concentrations in response to an oral glucose tolerance test (OGTT) with subsequent measures of ad libitum food intake and body weight change. Food intake analysis: Pima Indians (n=67, 63% male; body mass index (mean ± s.d.) 34.2 ± 9.4 kg m(-2)) with normal glucose regulation (NGR; fasting glucose libitum food intake measured over 3 days by an automated vending machine system. Weight change analysis: Pima Indians with NGR (n=339) who also participated in a longitudinal study of risks for type 2 diabetes and had follow-up weights. Food intake analysis: incremental area under the curve (iAUC) for insulin during the OGTT was negatively associated with mean daily ad libitum energy intake (DEI) (r=-0.26, P=0.04), calories consumed as percent weight-maintenance energy needs (%WMEN) (r=-0.38, P=0.002) and carbohydrate intake (gram per day) (r=-0.35, P=0.005). Adjustment for age and sex attenuated the association of iAUC with DEI (P=0.06) not with %WMEN and carbohydrate intake (P=0.005, P=0.008). Weight change analysis: after adjustment for age, sex, follow-up time and initial body weight, higher insulin iAUC predicted less absolute and percent weight change (β=-6.9, P=0.02; β=-0.08, P=0.008, respectively). In healthy Pima Indians with NGR, higher plasma iAUC during an OGTT predicted lower food intake and carbohydrate consumption and less weight gain. These data indicated a role for peripheral insulin as a negative feedback signal in the regulation of energy intake and body weight.

  13. A synthetic triacylated pseudo-dipeptide molecule promotes Th1/TReg immune responses and enhances tolerance induction via the sublingual route.

    Science.gov (United States)

    Mascarell, Laurent; Van Overtvelt, Laurence; Lombardi, Vincent; Razafindratsita, Alain; Moussu, Hélène; Horiot, Stéphane; Chabre, Henri; Limal, David; Moutel, Stéphane; Bauer, Jacques; Chiavaroli, Carlo; Moingeon, Philippe

    2007-12-21

    In this study, we tested two triacylated pseudo-dipeptidic molecules, OM-197-MP-AC and OM-294-BA-MP as candidate adjuvants for allergy vaccines. Both molecules induce human dendritic cell (h-DC) maturation and polarize naïve T cells toward the Th1 type with IFNgamma production. Only OM-294-BA-MP induces IL10 gene expression both in monocyte-derived DCs and CD4+ naïve T cells. Sublingual administration of OM-294-BA-MP plus the antigen enhances tolerance induction in BALB/c mice with established asthma to ovalbumin with an impact on both airways hyperresponsiveness and lung inflammation. Given its Th1/Treg polarizing properties, OM-294-BA-MP is a valid candidate for sublingual allergy vaccines.

  14. Central sensibility of human cases with different body mass during oral glucose tolerance test using functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Because of the limitation of technique, there are few researches on regulating function of central hypothalamus by metabolism, especially the researches on real-time function.OBJECTIVE: To evaluate the response of hypothalamus to oral glucose tolerance test (OGTT) in different body-weighted subjects by using functional magnetic resonance imaging (fMRI) so as to investigate the relationship between the sensitivity of hypothalamus in glycoregulation and disturbance of carbohydrate metabolism.DESIGN: Paired design.SETTING: Department of Radiology and Beijing Geriatrics Institute, Beijing Hospital, National Public Health Bureau.PARTICIPANTS: A total of twenty healthy volunteers were selected from Beijing Geriatrics Institute,National Public Health Bureau, including 10 subjects with obesity (5 males and 5 females; body mass >28.0 kg/m2) and 10 subjects with normal body mass (5 males and 5 females; body mass from 18.5 to 23.9 kg/m2). All subjects gave written informed consent before participating in the study.METHODS: fMRI study was performed on GE 1.5 T Signa Twinspeed Infinity with Excite. Each volunteer was ingested of glucose during the fMRI scan. T2* images were acquired using a single-shot gradient echo (EPI) technique. The parameters of EPI included: TR 3 000 ms, TE 40 ms, Flip angle 90 ° , field of view (FOV) 24 cm × 24 cm, thickness 5 mm, gap 0 mm, matrix 64 × 64, number of excitation 1. All 10 subjects with normal body mass underwent a repeat fMRI scan after consuming an equivalent amount of water without glucose on a separate day. The procedure for the fMRI scan with water intake was the same as for glucose ingestion. fMRI data were processed with Intensity Averaging Method.MAIN OUTCOME MEASURES: The central response of hypothalamus and feedback orientation during OGTT in different body-weighted subjects.RESULTS: An acute transient decrease of fMRI intensity in posterior inferior and anterior inferior of hypothalamus was observed in all

  15. Role of tumor necrosis factor-α and interleukin-1β in anorexia induction following oral exposure to the trichothecene deoxynivalenol (vomitoxin) in the mouse.

    Science.gov (United States)

    Wu, Wenda; Zhang, Haibin

    2014-01-01

    The trichothecene deoxynivalenol (DON), a foodborne mycotoxin found in grain-based foods, has been associated with human and animal food poisoning. Although induction of anorexia has been described as a hallmark of DON-induced toxicity in many animal species, the mechanistic basis for this adverse effect is not fully understood. The purpose of this research was to determine the role of two proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in DON-induced anorexia. In a nocturnal mouse food consumption model, DON-induced anorectic response occurred at 1 hr and lasted up to 6 hr. Similar anorectic effects were observed following acute administration of exogenous TNF-α and IL-1β. Oral exposure to DON at 5 mg/kg bw stimulated splenic and hepatic mRNA and plasma protein elevations of TNF-α and IL-1β that corresponded to anorexia induction. Pretreatment with the TNF-α receptor (TNFR) antagonist R-7050 dose-dependently attenuated both TNF-α- and DON-induced anorexia. While, the type 1 IL-1 receptor (IL-1R1) antagonist IL-1RA dose-dependently attenuated both IL-1β- and DON-induced anorexia. Taken together, the results suggest that both TNF-α and IL-1β play contributory role in anorexia induction following oral exposure to DON.

  16. Induction of protective immune responses against challenge of Actinobacillus pleuropneumoniae by oral administration with Saccharomyces cerevisiae expressing Apx toxins in pigs.

    Science.gov (United States)

    Shin, Min-Kyoung; Kang, Mi Lan; Jung, Myung Hwan; Cha, Seung-Bin; Lee, Won-Jung; Kim, Jung-Mi; Kim, Dae-Hyuk; Yoo, Han Sang

    2013-01-15

    Actinobacillus pleuropneumoniae is a causative agent of porcine pleuropneumonia, a highly contagious endemic disease of pigs worldwide, inducing significant economic losses worldwide. Apx toxins, which are correlated with the virulence of A. pleuropneumoniae, were expressed in Saccharomyces cerevisiae and its possible use as an oral vaccine has been confirmed in our previous studies using a murine model. The present study was undertaken to test the hypothesis that oral immunization using S. cerevisiae expressing either ApxI or ApxII could protect pigs against A. pleuropneumoniae as an effective way of inducing both mucosal and systemic immune responses. The surface-displayed ApxIIA#5 expressing S. cerevisiae was selected as an oral vaccine candidate by finding on induction of higher immune responses in mice after oral vaccination. The surface-displayed ApxIIA#5 expressing S. cerevisiae and the ApxIA expressing S. cerevisiae were developed to serve as an oral vaccine in pigs. The vaccinated pigs showed higher specific IgG- and IgA-related antibody activities than the non-treated control and vector control pigs. Additionally, the induced immune responses were found to protect pigs infected with A. pleuropneumoniae according to the analysis of clinical signs and the gross and microscopic pulmonary lesions. These results suggested that the surface-displayed ApxIIA#5 and ApxIA in S. cerevisiae might be a potential oral vaccine to protect pigs against porcine pleuropneumonia. Thus the present study is expected to contribute to the development of a live oral vaccine against porcine pleuropneumonia as an alternative to current conventional vaccines. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Induction of hapten-specific tolerance of human CD8+ urushiol (poison ivy)-reactive T lymphocytes.

    Science.gov (United States)

    Kalish, R S; Wood, J A

    1997-03-01

    The interaction of CD28 with B7 molecules (CD80 or CD86) is an essential second signal for both the activation of CD4+ T cells through the T-cell receptor and the prevention of anergy. We studied the requirement of hapten-specific human CD8+ cells for CD28 co-stimulation in recognition of hapten, and anergy induction. Urushiol, the immunogenic hapten of poison ivy (Toxicodendron radicans), elicits a predominantly CD8+ T-cell response. Autologous PBMC were pre-incubated with urushiol prior to fixation by paraformaldehyde. Fixed antigen-presenting cells were unable to present urushiol to human CD8+ urushiol-specific T cells. Addition of anti-CD28, however, overcame this antigen-presenting defect, enabling CD8+ cells to proliferate. Fixation of antigen-presenting cells prevents upregulation of B7, and addition of anti-CD28 substitutes for this signal. Proliferation of CD8+ T cells in response to urushiol was blocked by CTLA4Ig, a recombinant fusion protein that blocks CD28/B7 interactions. Preincubation of urushiol-specific CD8+ cells with fixed PBMC + urushiol for 7 d induced anergy. Anergic CD8+ cells were viable and able to proliferate in response to IL-2, but not in response to urushiol. Induction of anergy required the presence of urushiol, and pre-incubation with irradiated PBMC + urushiol did not have this effect. It is proposed that anergy was induced by presentation of urushiol by fixed PBMC, in the absence of adequate co-stimulation signals. Induction of anergy by blocking of co-stimulation could potentially induce clinical hyposensitization to haptens.

  18. Gene induction by desiccation stress in the entomopathogenic nematode Steinernema carpocapsae reveals parallels with drought tolerance mechanisms in plants.

    Science.gov (United States)

    Tyson, Trevor; Reardon, Wesley; Browne, John A; Burnell, Ann M

    2007-06-01

    The dauer juvenile (DJ) stage of the insect parasitic nematode Steinernema carpocapsae is the only stage in the life cycle which is capable of surviving outside its host and it is adapted for tolerating environmental stresses and for host finding. We have isolated 45 unique expressed sequence tags (ESTs) that are up-regulated in response to desiccation in S. carpocapsae DJs. The majority of these ESTs were co-expressed in response to desiccation and osmotic stress and were generally not induced in response to heat and cold stress. Thirty-two ESTs showed similarity to known sequences. Among these were sequences which encode putative signalling molecules or transcription factors, sequences which detoxify reactive oxygen species, two C-type lectin sequences, ESTs which encode membrane-associated proteins and seven distinct late embryogenic abundant (LEA) sequences. We also isolated 13 novel ESTs. These data show that the molecular response to desiccation stress in entomopathogenic nematode DJs is complex and parallels many of the adaptive changes which occur in drought tolerant plants during exposure to desiccation and osmotic stress. A notable feature of the desiccation response of plants is the number and diversity of hydrophilic LEA proteins synthesised in response to desiccation. All of the LEA sequences detected in animals to date, including those reported in this study, belong to LEA3 group. We show that S. carpocapsae expresses several novel sequences which encode putative hydrophilic and natively unfolded proteins. It is likely that these novel and putative proteins play an important role in desiccation tolerance, possibly by carrying out analogous roles in nematodes to those carried out by the other LEA protein classes in plants.

  19. Redox-dependent induction of antioxidant defenses by phenolic diterpenes confers stress tolerance in normal human skin fibroblasts: Insights on replicative senescence.

    Science.gov (United States)

    Carvalho, Ana C; Gomes, Andreia C; Pereira-Wilson, Cristina; Lima, Cristovao F

    2015-06-01

    Mild stress-induced hormesis represents a promising strategy for targeting the age-related accumulation of molecular damage and, therefore, for preventing diseases and achieving healthy aging. Fruits, vegetables, and spices contain a wide variety of hormetic phytochemicals, which may explain the beneficial health effects associated with the consumption of these dietary components. In the present study, the induction of cellular antioxidant defenses by the phenolic diterpenes carnosic acid (CA) and carnosol (CS) were studied in normal human skin fibroblasts, and insights into the aging process at the cellular level investigated. We observed that CA and CS induced several cytoprotective enzymes and antioxidant defenses in human fibroblasts, whose induction was dependent on the cellular redox state for CS and associated with Nrf2 signaling for both compounds. The stress response elicited by preincubation with CS conferred a cytoprotective action against a following oxidant challenge with tert-butyl hydroperoxide, confirming its hormetic effect. Preincubation of normal fibroblasts with CS also protected against hydrogen peroxide-induced premature senescence. Furthermore, cultivation of middle passage normal human skin fibroblasts in the presence of CS ameliorated the physiological state of cells during replicative senescence. Our results support the view that mild stress-induced antioxidant defenses by CS can confer stress tolerance in normal cells and may have important implications in the promotion of healthy aging.

  20. Transient systemic inflammation does not alter the induction of tolerance to gastric autoantigens by migratory dendritic cells.

    Science.gov (United States)

    Bourges, Dorothée; Ross, Ellen M; Allen, Stacey; Read, Simon; Houghton, Fiona J; Bedoui, Sammy; Boon, Louis; Gleeson, Paul A; van Driel, Ian R

    2014-06-01

    It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance.

  1. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study.

    Science.gov (United States)

    Burton, J P; Cowley, S; Simon, R R; McKinney, J; Wescombe, P A; Tagg, J R

    2011-09-01

    Streptococcus salivarius is naturally a predominant member of the human oropharynx and the commercial probiotic strain K12 has been consumed for more than a decade. The present study examines the health responses of human volunteers to oral ingestion of high doses of S. salivarius K12. A randomized group of 53 subjects received a dose of 1 × 10(10)cfu S. salivarius K12 (N=25) or placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine and saliva samples were collected at baseline and following treatment and analyzed, while the oral and gastrointestinal tolerance of the subjects to the dosing regimen was determined by use of questionnaires. Adverse events (AE)s were recorded for both groups. No statistically significant differences between the probiotic and placebo treated groups were detected in either the blood clinical chemistry or hematology results (P>0.05). The questionnaire responses of the subjects indicated that both treatments were well tolerated. The frequency and intensity of AEs was similar in the two groups. This data demonstrates that the daily ingestion of S. salivarius K12 over a 28-day period does not adversely affect the human host and supports the safety of its oral delivery in a food-based carrier. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Evaluation of a 1-h 75-g oral glucose tolerance test in the diagnosis of gestational diabetes

    Directory of Open Access Journals (Sweden)

    M.A.A. Campos

    2008-08-01

    Full Text Available In order to evaluate the performance of a 1-h 75-g oral glucose tolerance test (OGTT for the diagnosis of gestational diabetes mellitus (GDM, a cohort of 4998 women, 20 years or older, without previous diabetes being treated in prenatal care clinics in Brazil answered a questionnaire and performed a 75-g OGTT including fasting, 1-h and 2-h glucose measurements between their 24th and 28th gestational weeks. Pregnancy outcomes were transcribed from medical registries. GDM was defined according to WHO criteria (fasting: ≥126 mg/dL; 2-h value: ≥140 mg/dL and macrosomia as a birth weight equal to or higher than 4000 g. Areas under the receiver operator characteristic curve (AUC were compared and diagnostic properties of various cut-off points were evaluated. The AUCs for the prediction of macrosomia were 0.606 (0.572-0.637 for the 1-h and 0.589 (0.557-0.622 for the 2-h plasma glucose test. Similar predictability was demonstrable regarding combined adverse outcomes: 0.582 (0.559-0.604 for the 1-h test and 0.572 (0.549-0.595 for the 2-h test. When the 1-h glucose test was evaluated against a diagnosis of GDM defined by the 2-h glucose test, the AUC was 0.903 (0.886-0.919. The cut-off point that maximized sensitivity (83% and specificity (83% was 141 mg/dL, identifying 21% of the women as positive. A cut-off point of 160 mg/dL, with lower sensitivity (62%, had higher specificity (94%, labeling 8.6% as positive. Detection of GDM can be done with a 1-h 75-g OGTT: the value of 160 mg/dL has the same diagnostic performance as the conventional 2-h value (140 mg/dL. The simplification of the test may improve coverage and timing of the diagnosis of GDM.

  3. Induction of Th1-Type Immune Response by Chitosan Nanoparticles Containing Plasmid DNA Encoding House Dust Mite Allergen Der p 2 for Oral Vaccination in Mice

    Institute of Scientific and Technical Information of China (English)

    Guoping Li; Zhigang Liu; Bin Liao; Nanshan Zhong

    2009-01-01

    This study was to prepare the chitosan-pDer p 2 nanoparticles and to investigate the effect of chitosan-DNA nanoparticles on immune response in mice by oral delivery of chitosan-DNA nanoparticles. The nanoparticles were synthesized by complexing chitosan with plasmid DNA. The DNA was fully complexed into chitosan-DNA nanoparticles, suggesting a 100% encapsulation efficiency. Chitosan-DNA complex renders a significant protection of the plasmid. No effect on cell viability was observed in both cell types and average cell viability over 100% was obtained. Oral gene delivery with chitosan-DNA nanoparticles can generate a higher level expression of gene in vivo. Oral chitosan-pDer p 2 nanoparticles in BALB/c mice can induce IFN-γ in serum and prevent subsequent sensitization of Th2 cell-regulated specific IgE responses. The data indicate that the oral administration of chitosan-pDer p 2 nanoparticles results in the expression of Der p 2 in the epithelial cells of both stomach and small intestine and the induction of Th1-type immune response.

  4. [Selective induction of dog esophageal carcinomas by the restricted oral administration of N-ethyl-N-'-nitro-N-nitrosoguanidine with a projecting spout].

    Science.gov (United States)

    Tsukahara, Y; Fujita, M; Ohmichi, M; Ishii, T; Taguchi, T

    1989-08-01

    In order to establish an effective method to induce selectively experimental dog esophageal carcinoma, we compared the restricted oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) with projecting spout with the ad libitum oral administration of it. Five dogs were given a solution of ENNG at a concentration of 50mg/l with restricted oral administration with projecting spout for 52 weeks. In all of them, elevated type of esophageal lesions were endoscopically observed soon after the cessation of the ENNG administration. Histological examination revealed that besides the multiple squamous cell carcinomas of the esophagus, various degrees of dysplasias were seen. Two dogs had metastasizes to the regional lymph nodes and one dog had metastatic lesions in the lung. Gastric carcinomas were also seen in four dogs. Another five dogs were given ad libitum the same concentration of ENNG solution. Gastric carcinomas were induced in four dogs, but esophageal carcinomas were seen in small lesions in two dogs. The restricted oral administration of ENNG with projecting spout is a reliable method for the selective induction of esophageal carcinoma in dog.

  5. Reduced frequency of nickel allergy upon oral nickel contact at an early age

    DEFF Research Database (Denmark)

    Van Hoogstraten, I M; Andersen, Klaus Ejner; Von Blomberg, B M

    1991-01-01

    From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could...... the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed...... by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency...

  6. Preinduction incentive spirometry versus deep breathing to improve apnea tolerance during induction of anesthesia in patients of abdominal sepsis: A randomized trial

    Directory of Open Access Journals (Sweden)

    M Tripathi

    2013-01-01

    group 2 patients (48:44-58 s. Conclusions: IS in the preoperative period is superior to deep breathing sessions for improving apnea tolerance during induction of anesthesia in abdominal sepsis patients.

  7. Mechanism-based population modelling for assessment of L-cell function based on total GLP-1 response following an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Møller, Jonas B.; Jusko, William J.; Gao, Wei;

    2011-01-01

    GLP-1 is an insulinotropic hormone that synergistically with glucose gives rise to an increased insulin response. Its secretion is increased following a meal and it is thus of interest to describe the secretion of this hormone following an oral glucose tolerance test (OGTT). The aim of this study...... was to build a mechanism-based population model that describes the time course of total GLP-1 and provides indices for capability of secretion in each subject. The goal was thus to model the secretion of GLP-1, and not its effect on insulin production. Single 75 g doses of glucose were administered orally....... The individual estimates of absorption rate constants were used in the model for GLP-1 secretion. Estimation of parameters was performed using the FOCE method with interaction implemented in NONMEM VI. The final transit/indirect-response model obtained for GLP-1 production following an OGTT included two...

  8. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  9. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome

    DEFF Research Database (Denmark)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn

    2016-01-01

    BACKGROUND: Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism......-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. METHODS: A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study...

  10. Efficacy and tolerability of sequential intravenous/oral moxifloxacin therapy in pneumonia: results of the first post-marketing surveillance study with intravenous moxifloxacin in hospital practice.

    Science.gov (United States)

    Barth, J; Stauch, K; Landen, H

    2005-01-01

    This study aimed to investigate the efficacy, safety and tolerability of sequential intravenous (IV)/oral therapy with moxifloxacin in pneumonia under general hospital treatment conditions. Patients with pneumonia were documented in this non-interventional multicentre study. The patients were treated with IV moxifloxacin or moxifloxacin sequential therapy (IV and oral) in hospitals throughout Germany. Exclusion criteria were limited to the contraindications mentioned in the summary of product characteristics. The participating hospital-based physicians documented the patients' demography, anamnesis, antibiotic pretreatment, concomitant diseases and medications. Moxifloxacin therapy and symptom status were recorded daily up to the ninth day and on the last day of treatment. The physicians assessed the efficacy and tolerability of IV moxifloxacin therapy and reported all adverse events observed within the treatment period. The 1749 documented patients had a mean age of 66.2 (SD 15.5) years; 56.4% were males and 43.5% females. The majority (99.3%) were treated with moxifloxacin 400mg once daily. On average, moxifloxacin was given for 7.6 days (SD 3.2). In cases of sequential therapy (78.9% of patients), IV moxifloxacin was switched to oral moxifloxacin after a mean of 4.1 days (SD 1.8). Moxifloxacin produced a significant clinical improvement in 58.2% of patients by day 3 of therapy, in 84.2% by day 5 and in 89.4% by day 7. Recovery occurred in 27.0% of patients by day 5, in 54.0% by day 7 and in 87.0% by day 14. It took a mean of 3.4 days (SD 1.9) until improvement and 7.2 days (SD 3.0) until cure. Overall efficacy of IV moxifloxacin therapy was rated by the physicians as 'very good' or 'good' in 82.9% of patients. Tolerability was rated in 94.3% of patients as 'very good' or 'good'. Adverse events were recorded for 92 (5.3%) patients, but events were considered by the attending physician to be related to moxifloxacin therapy for only 45 patients (2.6%). IV

  11. Tolerance induction and reversal of diabetes in mice transplanted with human embryonic stem cell-derived pancreatic endoderm.

    Science.gov (United States)

    Szot, Gregory L; Yadav, Mahesh; Lang, Jiena; Kroon, Evert; Kerr, Justin; Kadoya, Kuniko; Brandon, Eugene P; Baetge, Emmanuel E; Bour-Jordan, Hélène; Bluestone, Jeffrey A

    2015-02-05

    Type 1 diabetes (T1D) is an autoimmune disease caused by T cell-mediated destruction of insulin-producing β cells in the islets of Langerhans. In most cases, reversal of disease would require strategies combining islet cell replacement with immunotherapy that are currently available only for the most severely affected patients. Here, we demonstrate that immunotherapies that target T cell costimulatory pathways block the rejection of xenogeneic human embryonic-stem-cell-derived pancreatic endoderm (hESC-PE) in mice. The therapy allowed for long-term development of hESC-PE into islet-like structures capable of producing human insulin and maintaining normoglycemia. Moreover, short-term costimulation blockade led to robust immune tolerance that could be transferred independently of regulatory T cells. Importantly, costimulation blockade prevented the rejection of allogeneic hESC-PE by human PBMCs in a humanized model in vivo. These results support the clinical development of hESC-derived therapy, combined with tolerogenic treatments, as a sustainable alternative strategy for patients with T1D.

  12. Tolerization of an established αb-crystallin-reactive T-cell response by intravenous antigen

    NARCIS (Netherlands)

    Verbeek, R.; Mark, K. van der; Wawrousek, E.F.; Plomp, A.C.; Noort, J.M. van

    2007-01-01

    Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an e

  13. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

    Science.gov (United States)

    Kreuz, W; Escuriola Ettingshausen, C; Vdovin, V; Zozulya, N; Plyushch, O; Svirin, P; Andreeva, T; Bubanská, E; Campos, M; Benedik-Dolničar, M; Jiménez-Yuste, V; Kitanovski, L; Klukowska, A; Momot, A; Osmulskaya, N; Prieto, M; Šalek, S Z; Velasco, F; Pavlova, A; Oldenburg, J; Knaub, S; Jansen, M; Belyanskaya, L; Walter, O

    2016-01-01

    Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  14. The Effect of Spermidine on Cold Tolerance Induction in Cucumber Seedlings ‘Cv. Super-Dominus’

    Directory of Open Access Journals (Sweden)

    Golnar GhazianTafrishi

    2017-02-01

    expect for shoot dry weight. Spermidine enhances chilling tolerance in cucumber by prohibiting the activity of NADPH oxidase. The capacity of PAs to enhance the tolerance of cucumber to chilling injury is attributed to the scavenging of H2O2 production under chilling condition. Conclusion: Results showed that root and shoot length and weight, root and leaf electrical leakage and chlorophyll content of leaf adversely affected by chilling stress. Using 0.25 mg/L spermidine modulates plant responses to chilling stress. There was no significant difference between 0.25 and 0.5 mg/L spermidine in respect of measured traits. But all measured traits adversely affected using 0.75 mg/L spermidine at both 6 and 12°C.

  15. Successful immune tolerance induction with low-dose coagulation factor VIII in a patient with hemophilia A from a developing country.

    Science.gov (United States)

    Ay, Yilmaz; Ersin, Toret; Yesim, Oymak; Hilkay, Karapinar Tuba; Dilek, Ince; Gulcihan, Ozek; Ahmet, Koc

    2016-09-01

    Inhibitor development is the most frequent and serious complication of the treatment in patients with hemophilia. Immune tolerance induction (ITI) is the only option of treatment for the eradication of factor VIII (FVIII) inhibitor. We would like to present our case with hemophilia whose FVIII inhibitor eradication was done by a low-dose ITI regimen. Our patient has been applied on-demand therapy until 8 years of age. Secondary prophylaxis was began because of having hemophilic arthropathy. A low titer of FVIII inhibitor (4.2 BU/ml) was detected in the fifth month of the prophylaxis. The peak inhibitor titer of patient was 4.6 BU/ml, and there was no decrease in inhibitor titer in the follow-up duration. The low-dose ITI (50 IU/kg, 3 days a week) was started. His inhibitor level was detected negative and the recovery test was ameliorated in the 15th of the ITI therapy. High-dose regimen ITI could not be given particularly in developing countries such as Turkey in view of the high cost of treatment. Patients who had good risk factors might be successfully treated by using low-dose ITI regimen as effective as high-dose ITI regimen.

  16. A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of DS-3801b, a Motilin Receptor Agonist, in Healthy Subjects.

    Science.gov (United States)

    Dennie, Justin; Atiee, George; Warren, Vance; Tao, Ben; Morimoto, Kiyoshi; Senaldi, Giorgio

    2017-09-01

    DS-3801b is an orally active, nonmacrolide, selective motilin receptor agonist. The aim of this 2-part first-in-human study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamic effects on proximal and distal gastrointestinal (GI) motility of single oral doses of DS-3801b in healthy subjects. The (13) C-octanoate breath test was used to assess gastric emptying (GE), a measure of proximal GI motility. The time to first bowel movement (TTFBM) and the consistency of the first bowel movement according to the Bristol Stool Scale (BSS) were recorded to assess distal GI motility. In part A, 48 subjects received single oral doses of DS-3801b from 1 to 100 mg or placebo (6 DS-3801b, 2 placebo per cohort). In part B, 12 subjects received 50 mg of DS-3801b or placebo to assess GE. DS-3801b is safe and generally well tolerated after doses up to 50 mg, resulting in mild, predominantly GI adverse events. DS-3801a plasma concentrations increase with increasing doses; however, Cmax increases greater than dose-proportionally, whereas AUC increases less than dose-proportionally. The double peaks observed are consistent with multiple absorption sites. Results of the (13) C-octanoate breath test indicate that DS-3801b accelerates GE. Fifty milligrams of DS-3801b resulted in a 20.8% median reduction in GE T1/2 and a 20.6% median reduction in GE Tlag compared with placebo. However, this increase in proximal GI motility was not accompanied by an effect on distal GI motility, as indicated by no significant differences in TTFBM and BSS values across DS-3801b dose levels or compared with placebo. © 2017, The American College of Clinical Pharmacology.

  17. On the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test.

    Directory of Open Access Journals (Sweden)

    Lin-jie Lu

    Full Text Available AIMS: This study is to estimate the status and comparison of glucose intolerance in female breast cancer patients at initial diagnosis and during chemotherapy through an oral glucose tolerance test (OGTT, as well as to learn the effect of chemotherapy on the glucose metabolism of breast cancer patients. METHODS: All the 79 breast cancer patients at initial diagnosis, with the mean age of 53.2 years, and 96 breast cancer patients before the 5th or 6th cycle of chemotherapy, with the mean age of 51.5 years, participated in the study from December 2012 to October 2013. After an overnight fast, participants underwent OGTT test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance in them. Previously diagnosed diabetes among the female breast cancer patients was determined on the self-report and the medical record. RESULTS: The overall incidences of total normal glucose tolerance, prediabetes, diabetes in female breast cancer patients at initial diagnosis and during chemotherapy were 24.1% and 38.5% (p0.05, respectively, and the differences of normal glucose tolerance and prediabetes instead of diabetes between the two groups were statistically significant. About 84% of the total diabetes and prediabetes in the female breast cancer patients at initial diagnosis and 79.7% of those during chemotherapy need to be diagnosed with OGTT. CONCLUSIONS: Breast cancer patients have high incidences of diabetes and prediabetes. After chemotherapy even with steroids, some breast cancer patients with abnormal glucose metabolism may even become normal. Isolated hyperglycemia 2 hours after glucose loading is common, and OGTT should be made for breast cancer patients at initial diagnosis and during chemotherapy.

  18. Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women

    DEFF Research Database (Denmark)

    Jensen, Dorte Møller; Damm, P; Sørensen, B

    2003-01-01

    AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk....../l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol....../l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes...

  19. Antiproliferation and Induction of Apoptosis in Ca9-22 Oral Cancer Cells by Ethanolic Extract of Gracilaria tenuistipitata

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-09-01

    Full Text Available The water extract of Gracilaria tenuistipitata have been found to be protective against oxidative stress-induced cellular DNA damage, but the biological function of the ethanolic extracts of G. tenuistipitata (EEGT is still unknown. In this study, the effect of EEGT on oral squamous cell cancer (OSCC Ca9-22 cell line was examined in terms of the cell proliferation and oxidative stress responses. The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose-response manner (p < 0.0001. The annexin V intensity and pan-caspase activity of EEGT-treated OSCC cells were significantly increased in a dose-response manner (p < 0.05 to 0.0001. EEGT significantly increased the reactive oxygen species (ROS level (p < 0.0001 and decreased the glutathione (GSH level (p < 0.01 in a dose-response manner. The mitochondrial membrane potential (MMP of EEGT-treated OSCC cells was significantly decreased in a dose-response manner (p < 0.005. In conclusion, we have demonstrated that EEGT induced the growth inhibition and apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion, caspase activation, and mitochondrial depolarization. Therefore, EEGT may have potent antitumor effect against oral cancer cells.

  20. Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by ethanolic extract of Gracilaria tenuistipitata.

    Science.gov (United States)

    Yeh, Chi-Chen; Tseng, Chao-Neng; Yang, Jing-Iong; Huang, Hurng-Wern; Fang, Yi; Tang, Jen-Yang; Chang, Fang-Rong; Chang, Hsueh-Wei

    2012-09-11

    The water extract of Gracilaria tenuistipitata have been found to be protective against oxidative stress-induced cellular DNA damage, but the biological function of the ethanolic extracts of G. tenuistipitata (EEGT) is still unknown. In this study, the effect of EEGT on oral squamous cell cancer (OSCC) Ca9-22 cell line was examined in terms of the cell proliferation and oxidative stress responses. The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose-response manner (p < 0.0001). The annexin V intensity and pan-caspase activity of EEGT-treated OSCC cells were significantly increased in a dose-response manner (p < 0.05 to 0.0001). EEGT significantly increased the reactive oxygen species (ROS) level (p < 0.0001) and decreased the glutathione (GSH) level (p < 0.01) in a dose-response manner. The mitochondrial membrane potential (MMP) of EEGT-treated OSCC cells was significantly decreased in a dose-response manner (p < 0.005). In conclusion, we have demonstrated that EEGT induced the growth inhibition and apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion, caspase activation, and mitochondrial depolarization. Therefore, EEGT may have potent antitumor effect against oral cancer cells.

  1. Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction.

    Science.gov (United States)

    Liu, Chia-Ming; Peng, Chih-Yu; Liao, Yi-Wen; Lu, Ming-Yi; Tsai, Meng-Lun; Yeh, Jung-Chun; Yu, Chuan-Hang; Yu, Cheng-Chia

    2017-01-01

    Cancer stem cells (CSCs) are deemed as the driving force of tumorigenesis in oral squamous cell carcinomas (OSCCs). In this study, we investigated the chemotherapeutic effect of sulforaphane, a dietary component from broccoli sprouts, on targeting OSCC-CSCs. The effect of sulforaphane on normal oral epithelial cells (SG) and sphere-forming OSCC-CSCs isolated from SAS and GNM cells was examined. ALDH1 activity and CD44 positivity of OSCC-CSCs with sulforaphane treatment was assessed by flow cytometry analysis. In vitro and in vivo tumorigenicity assays of OSCC-CSCs with sulforaphane treatment were presented. We observed that the sulforaphane dose-dependently eliminated the proliferation rate of OSCC-CSCs, whereas the inhibition on SG cells proliferation was limited. Cancer stemness properties including self-renewal, CD44 positivity, and ALDH1 activity were also decreased in OSCC-CSCs with different doses of sulforaphane treatment. Moreover, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts. Sulforaphane treatment resulted in a dose-dependent increase in the levels of tumor suppressive miR200c. These lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo. Copyright © 2016. Published by Elsevier B.V.

  2. Effective immunity to dental caries: selective induction of secretory immunity by oral administration of Streptococcus mutans in rodents.

    Science.gov (United States)

    Michalek, S M; McGhee, J R; Arnold, R R; Mestecky, J

    1978-01-01

    1) The selective induction of secretory antibody is antigen dose dependent. A dose of 10(7) or 10(8) S. mutans CFU (per gram of diet) elicited a significant response, while a higher dose (10(9) CFU/gram) resulted in an apparent state of unresponsiveness. 2) A lowly virulent mutant of S. mutans 6715 (C4) induced protective s-IgA antibodies against challenge with a highly virulent species (C211). Cross protection among serotypes of S. mutans has been achieved. 3) Bovine milk with antibodies to S. mutans significantly reduced the level of caries lesions in rats fed this lyophilized milk and challenged with the homologous, virulent S. mutans strains.

  3. Effects of Oral Administration of Moringa oleifera Lam on Glucose Tolerance in Goto-Kakizaki and Wistar Rats.

    Science.gov (United States)

    Ndong, Moussa; Uehara, Mariko; Katsumata, Shin-Ichi; Suzuki, Kazuharu

    2007-05-01

    Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30-60 min and 60-120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats.

  4. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    Science.gov (United States)

    Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  5. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    Directory of Open Access Journals (Sweden)

    Wichai Aekplakorn

    2015-01-01

    Full Text Available Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG and the 2 hr postprandial glucose tolerance test (OGTT in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG or impaired glucose tolerance (IGT, and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8% individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.. The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed.

  6. Induction of matrix metalloproteinases and TLR2 and 6 in murine colon after oral exposure to Mycobacterium avium subsp. paratuberculosis.

    Science.gov (United States)

    Roderfeld, Martin; Koc, Arzu; Rath, Timo; Blöcher, Sonja; Tschuschner, Annette; Akineden, Ömer; Fischer, Marta; von Gerlach, Susanne; Goethe, Ralph; Eckelt, Elke; Meens, Jochen; Bülte, Michael; Basler, Tina; Roeb, Elke

    2012-06-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in Crohn's disease. Recent evidence suggests that MAP can induce the expression of Matrix Metalloproteinases (MMPs), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within the present study, we analysed whether oral MAP exposure can induce colonic MMP expression in vivo. In MAP exposed mice MAP and spheroplasts were visualized in intramucosal leukocyte aggregates. MAP exposed mice exhibited a higher colonic expression of Mmp-2, -9, -13, -14, Timp-1, Tlr2, Tlr6, Il-1β, and Tnf-α. Cell clusters of MMP-9 positive cells adjacent to intramucosal leukocyte aggregates and CD45(+) leukocytes were identified as the major cellular sources of MMP-9. Enhanced TLR2 expression was visualized on the luminal side of colonic enterocytes. Although MAP exposure did not lead to macroscopic intestinal inflammation, the observed MAP spheroplasts in intramucosal leukocyte aggregates together with increased colonic expression of toll-like receptors, pro-inflammatory cytokines, and MMPs upon MAP exposure represents a part of the host immune response towards MAP.

  7. Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts.

    Science.gov (United States)

    Ni, Wei-Feng; Tsai, Chung-Hung; Yang, Shun-Fa; Chang, Yu-Chao

    2007-07-01

    Nuclear factor-kappa B (NF-kappaB) is considered to be important in many inflammatory and immune responses. The aim of this study was to compare NF-kappaB expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of NF-kappaB expression. Seventeen OSF and six normal buccal mucosa specimens were examined by immunohistochemistry. Primary human buccal mucosal fibroblasts (BMFs) were established and challenged with safrole, a major polyphenolic compound in the influorescence of Piper betel, by cytotoxicity and western blot assays. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, cyclooxygenase-2 (COX-2) inhibitor NS-398, dexamethasone, and cyclosporin A were added to find the possible mechanism. NF-kappaB expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Safrole was cytotoxic to BMFs in a dose-dependent manner (psafrole (psafrole induced-NF-kappaB expression (psafrole in fibroblasts may be mediated by ERK activation and COX-2 signal transduction pathway.

  8. Oral combined therapy with probiotics and alloantigen induces B cell-dependent long-lasting specific tolerance.

    Science.gov (United States)

    Mercadante, Ana C T; Perobelli, Suelen M; Alves, Ana P G; Gonçalves-Silva, Triciana; Mello, Wallace; Gomes-Santos, Ana C; Miyoshi, Anderson; Azevedo, Vasco; Faria, Ana M C; Bonomo, Adriana

    2014-02-15

    Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (graft-versus-leukemia [GVL]), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on nonspecific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. In this study, we propose an alternative approach to specifically suppress GVHD while sparing the GVL, based on oral treatment of transplant donors with recipient Ags, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). We show that treatment of C57BL/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57BL/6 × BAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third-party Ags. The protection is specific, long lasting and dependent on donor IL-10-sufficient B cells activity, which induces regulatory T cells in the host. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected to transplantation.

  9. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults.

    Science.gov (United States)

    Iida, Tetsuo; Kishimoto, Yuka; Yoshikawa, Yuko; Hayashi, Noriko; Okuma, Kazuhiro; Tohi, Mikiko; Yagi, Kanako; Matsuo, Tatsuhiro; Izumori, Ken

    2008-12-01

    An examination was conducted to verify D-psicose suppressed the elevation of blood glucose and insulin concentration in a dose-dependent manner under the concurrent administration of maltodextrin and D-psicose to healthy humans. Twenty subjects aged 20-39 y, 11 males and 9 females were recruited. A load test of oral maltodextrin was conducted as a randomized single blind study. The subjects took one of five test beverages (7.5 g D-psicose alone, 75 g maltodextrin alone, 75 g maltodextrin +2.5, 5 or 7.5 g D-psicose). Blood was collected before an intake and at 30, 60, 90 and 120 min after an intake. Intervals of administration were at least 1 wk. The load test with 75 g maltodextrin showed significant suppressions of the elevation of blood glucose and insulin concentration under the doses of 5 g or more D-psicose with dose dependency. An independent administration of 7.5 g D-psicose had no influence on blood glucose or insulin concentration. D-Psicose is considered efficacious in the suppression of the elevation of blood glucose concentration after eating in humans.

  10. Biofilm formation enhances the oxygen tolerance and invasiveness of Fusobacterium nucleatum in an oral mucosa culture model.

    Science.gov (United States)

    Gursoy, Ulvi Kahraman; Pöllänen, Marja; Könönen, Eija; Uitto, Veli-Jukka

    2010-07-01

    The present study evaluates the survival capability of Fusobacterium nucleatum strains in an aerobic environment and compares the invasive capability of F. nucleatum in biofilm and planktonic forms in an organotypic cell culture (OCC) model. Biofilms of F. nucleatum American Type Culture Collection (ATCC) 25586 or Anaerobe Helsinki Negative (AHN) 9508 were produced by culturing on semipermeable membranes on brucella agar plates. The oxygen tolerance of the F. nucleatum strains was examined by incubating 3-day-old anaerobically grown biofilms in an aerobic environment (CO(2) [5% in air] incubator) for an additional 48 hours. The OCC model was constructed by seeding keratinocytes on a fibroblast-containing collagen gel. In invasion assays, a 3-day-old anaerobically grown biofilm (and planktonic bacteria in solution as the control) was placed upside down on the top of OCC and incubated under 5% CO(2) for 24 hours. Invasion of the bacteria and morphologic changes in OCC were assessed using hematoxylin and eosin, Ki-67, and periodic acid-Schiff stainings. In biofilms, both F. nucleatum strains continuously increased their cell numbers in an aerobic environment for 48 hours. After incubating the bacterial biofilm in contact with the OCC model, F. nucleatum AHN 9508 was able to pass through the epithelial/basement membrane barrier and invade the collagen matrix. The invasiveness of biofilm F. nucleatum ATCC 25586 was limited to the epithelium. Cytotoxic effects and invasiveness of F. nucleatum on the OCC were much stronger when the bacteria were in biofilms than in the planktonic form. Biofilm formation regulates the survival and invasiveness of F. nucleatum in an aerobic environment.

  11. Solução oral escalonada de misoprostol para indução do parto: estudo piloto Titrated oral solution of misoprostol for labour induction: a pilot study

    Directory of Open Access Journals (Sweden)

    Alex Sandro Rolland Souza

    2010-05-01

    Full Text Available OBJETIVO: avaliar a efetividade e a segurança da administração de uma nova formulação de misoprostol em solução por via oral, com doses escalonadas, para indução do parto de feto vivo a termo. MÉTODOS: realizou-se um estudo multicêntrico, do tipo ensaio clínico, aberto, não-randomizado, no período de Julho a Dezembro de 2008. Foram incluídas 30 pacientes com indicação de indução do trabalho de parto, a termo, com feto vivo, índice de Bishop 5. Foram excluídas mulheres com cicatriz uterina, cardiotocografia alterada, gestação múltipla, restrição de crescimento fetal, hemorragia genital e presença de tumores, ulcerações ou malformações genitais. A dose inicial da solução oral foi de 20µg/h de misoprostol, nas primeiras 6 horas, aumentando em 20µg/h de misoprostol a cada 6 horas, se o trabalho de parto não fosse deflagrado, até uma dose máxima de 80µg/h, nas primeiras 24 horas, mantendo a dose máxima (80µg/h por mais 24 horas, se necessário. RESULTADOS: o trabalho de parto foi induzido satisfatoriamente em 96,7% das gestantes. O intervalo entre a primeira dose e o início das contrações uterinas foi de 3,8±1,8 horas, enquanto o intervalo entre a dose inicial e o parto variou entre 6 e 24 horas. A frequência de parto vaginal foi de 80% (n=24. A maioria das gestantes iniciou o trabalho de parto com a dose de 20µg/h (60%; n=18. A taquissistolia ocorreu em 13,3% das gestações e líquido meconial foi detectado em 20% dos casos. Houve dois casos de escore de Apgar PURPOSE: to test effectiveness and safety of the oral administration of a new misoprostol formulation in titrated doses for the induction of delivery of a live fetus at term. METHODS: an open pilot multicenter, non-randomized clinical trial was conducted from July to December 2008. A total of 30 patients with indications for induction of labor were included. The patients had a live fetus, Bishop score 5. Exclusion criteria were previous uterine

  12. Comparison of oral glucose tolerance tests and mixed meals in patients with apparent idiopathic postabsorptive hypoglycemia: absence of hypoglycemia after meals.

    Science.gov (United States)

    Charles, M A; Hofeldt, F; Shackelford, A; Waldeck, N; Dodson, L E; Bunker, D; Coggins, J T; Eichner, H

    1981-06-01

    The relationship between symptoms of idiopathic postabsorptive hypoglycemia and glucose homeostasis was evaluated by giving oral glucose tolerance tests (OGTT) and mixed meals to 18 patients and 16 controls. Chemical hypoglycemia after OGTT occurred as often in patients referred because of possible hypoglycemia symptoms, 18 out of 80 (23%), as in controls, 4 out of 16 (25%). After glucose, patients showed both clinical and chemical hypoglycemia (mean +/- SE plasma glucose, 48 +/- 3 mg/dl), but insulin, glucagon, and growth hormone responses were similar to controls. After mixed meals, no chemical hypoglycemia occurred in patients (mean plasma glucose, 79 +/- 3 mg/dl), yet 14 out of 18 (78%) had symptoms and/or signs consistent with hypoglycemia. No abnormality of glucose homeostasis was observed after meals that could account for symptoms or signs experienced by patients with idiopathic postabsorptive hypoglycemia. Since factors other than hypoglycemia appear to be involved, the disorder should be termed the idiopathic postprandial syndrome to avoid the connotation of chemical hypoglycemia.

  13. Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys.

    Science.gov (United States)

    Cockcroft, Emma Joanne; Williams, Craig Anthony; Jackman, Sarah Rebecca; Armstrong, Neil; Barker, Alan R

    2017-06-01

    Assessment of plasma insulin and glucose outcomes is important in paediatric studies aimed at reducing future risk of type 2 diabetes and cardiovascular disease. The aims of this study are to determine the between-method agreement and the day-to-day reliability of fasting and oral glucose tolerance test (OGTT)-derived estimates of insulin sensitivity and β-cell function in healthy boys. Fasting and OGTT assesments of insulin resistance and β-cell function were performed on 28 boys (12.3±2.9 years). Measurements were repeated after 1 week (fasting, n=28) and 1 day (OGTT, n=8). Agreement between estimates of insulin resistance and β-cell function was examined using Pearson's correlation coefficient. Reliability was assessed using change in the mean, Pearson's correlation coefficient, and typical error expressed as a coefficient of variation (CV). The Matsuda index was positively related with QUICKI (r=0.88, P0.05). For reliability, QUICKI had the lowest CV% for the fasting (4.7%) and the Cederholm index for the OGTT (6.4%) estimates. The largest CV% was observed in fasting insulin (30.8%) and insulinogenic index 30' (62.5%). This study highlights differences in between-method agreement and day-to-day reliability for estimates of insulin resistance in youth. The low CV supports the use of the FGIR (fasting) and Cederholm (OGTT) indices in this population. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Delphinidin-Rich Maqui Berry Extract (Delphinol® Lowers Fasting and Postprandial Glycemia and Insulinemia in Prediabetic Individuals during Oral Glucose Tolerance Tests

    Directory of Open Access Journals (Sweden)

    Jorge L. Alvarado

    2016-01-01

    Full Text Available Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through three possible mechanisms: by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity.

  15. Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study.

    Science.gov (United States)

    Shen, Songying; Lu, Jinhua; Zhang, Lifang; He, Jianrong; Li, Weidong; Chen, Niannian; Wen, Xingxuan; Xiao, Wanqing; Yuan, Mingyang; Qiu, Lan; Cheng, Kar Keung; Xia, Huimin; Mol, Ben Willem J; Qiu, Xiu

    2017-02-01

    There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22-28weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30-1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1h, and 2h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P=0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1mmol/l), irrespective of 1h or 2h glucose levels. A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Comparative Evaluation of Whole Body and Hepatic Insulin Resistance Using Indices from Oral Glucose Tolerance Test in Morbidly Obese Subjects with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Kamran Qureshi

    2010-01-01

    Full Text Available Nonalcoholic Fatty Liver Disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR. Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR. However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS, Quantitative Insulin Sensitivity Check Index (QUICKI for hepatic IR and Insulin Sensitivity Index (ISI0,120, and Whole Body Insulin Sensitivity Index (WBISI for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT. We used these indices as noninvasive methods of IR (inverse of insulin sensitivity estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL and Non-Alcoholic Steatohepatitis (NASH based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.

  17. [Alcohol tolerance in patients with non-insulin-dependent diabetes (type 2) treated orally with drugs--derivatives of sulphonylurea].

    Science.gov (United States)

    Lao, B; Czyzyk, A; Szutowski, M; Szczepanik, Z

    1993-06-01

    The oral ethanol loading test (0.5 g per kg b.m. given as 40% solution) was carried out in 5 groups, each of 10 patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide 0.5 t.i.d., chlorpropamide 0.5 once daily morning, glibornuride 0.025 t.i.d, glibenclamide 0.005 t.i.d. and glipizide 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentration of ethanol, acetaldehyde, pyruvate, lactate, carbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism. All studied drugs intensified to a similar degree the alcohol-induced hypoglycaemia, but had no significant effect on the decrease of blood pyruvate level neither on the increase of blood lactate level. They didn't change the post-alcohol decrease of blood bicarbonate and pH, and didn't modify the behaviour of partial gas pressure. There was also no difference between pooled groups of patients with positive and negative thermographic reaction

  18. Papel da indução de tolerância oral no remodelamento de vias aéreas e na expressão da óxido nítrico sintase neuronal

    OpenAIRE

    Viviane Christina Ruiz

    2006-01-01

    INTRODUÇÃO: A indução de tolerância oral atenua a resposta inflamatória e a produção de anticorpos anafiláticos secundários presentes em quadros alérgicos pulmonares tanto em humanos quanto em modelos experimentais. Nestas situações, a modulação do remodelamento brônquico e o papel do óxido nítrico não foram previamente estudados. OBJETIVOS: 1. Desenvolver dois modelos de tolerância oral em cobaias com inflamação crônica pulmonar caracterizando: mecânica pulmonar, hiper-responsividade a metac...

  19. Antitumor activity of Papua’s Myrmecodia pendans in human oral tongue squamous cell carcinoma cell line through induction of cyclin-dependent kinase inhibitor p27Kip1 and suppression of cyclin E

    Directory of Open Access Journals (Sweden)

    Supriatno DRG

    2014-03-01

    Full Text Available Oral tongue squamous cell carcinoma (OTSCC is one of the most common cancers encountered in Indonesia, due to the prevalent habits of tobacco chewing, alcohol drinking and smoking. Oral tongue cancer is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. Interestingly, treatment options for this cancer are limited. The aim of this study was to examine the antitumor activity of Papua’s Myrmecodia pendans (ant nest plant in a human oral tongue squamous cell carcinoma cell line (B88 and to explore the possible mechanism in it. In the present study, B88 cells were treated with various concentration of ethanol extract of Papua’s M. pendans. The results revealed that B88 cells treated with Papua’s M. pendans were remarkable suppressed in cell growth and cell invasion, and had a significant induction of apoptosis characterized by an increase in activation of caspase-3 and -9. Furthermore, up-regulation of p27Kip1 and down-regulation of cyclin E protein was detected in B88 cells treated with Papua’s M. pendans. These results indicated that Papua’s M. pendans exhibited a high potential antitumor activity in human oral tongue squamous cell carcinoma through induction of p27Kip1 and suppression of cycline E.

  20. 血友病A伴抑制物一例及其免疫耐受诱导治疗探讨%Immune tolerance induction in a severe hemophilia A patient with inhibitor

    Institute of Scientific and Technical Information of China (English)

    张磊; 杨仁池; 薛峰; 刘晓帆; 周泽平; 刘永泽; 田萌苏; 沈琳; 许剑辉; 张宏丽

    2010-01-01

    目的 探讨血友病A伴抑制物的免疫耐受诱导(immune tolerance induction,ITI)治疗,提高血友病A伴抑制物患者的诊疗水平.方法 对重型血友病A患者用APTT标准曲线一期法测定凝血因子Ⅷ(FⅧ)活性(FⅧ∶C);用Bethesda法定量测定FⅧ抗体;用长距离PCR方法检测内含子22倒位.结果 经检测发现患者为FⅧ基因22内含子倒位;ITI治疗3个月后,患者FⅧ抑制物滴度下降为0,输注FⅧ后回收率>66%,治疗6个月后达到抑制物清除标准,停止治疗.结论 该患者是国内首例采用ITI成功治疗血友病A伴抑制物的病例,ITI是目前最有希望根除血友病抑制物的方法.%Objective To explore the immune tolerance induction (ITI) in a severe hemophilia A sayed by one-stage method and FⅧ antibody by Bethesda method. Mutation screening of FⅧ gene intron 22 inversion was performed using LD-PCR. Results FⅧ gene intron 22 inversion was detected in this patient.Clinical tolerance to FⅧ was successfully induced after administration of the ITI regimen combined with immunosuppression. A fall of inhibitor titer from 8 BU to 0 BU after treatment for 3 months, and in vivo FⅧ recovery ( > 66% ) was normalized. The patient had no bleeding episode in the following 6 months. Conclusion This is the first case report on successful immune tolerance induction therapy in Chinese hemophilia A patient. ITI is the most effective therapy for hemophilia A with inhibitor.

  1. Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics--results from single oral dose studies in healthy volunteers.

    Science.gov (United States)

    Stoch, S Aubrey; Zajic, Stefan; Stone, Julie A; Miller, Deborah L; van Bortel, Lucas; Lasseter, Kenneth C; Pramanik, Barnali; Cilissen, Caroline; Liu, Qi; Liu, Lida; Scott, Boyd B; Panebianco, Deborah; Ding, Yu; Gottesdiener, Keith; Wagner, John A

    2013-05-01

    To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of odanacatib (ODN), a cathepsin K inhibitor, in humans. Two double-blind, randomized, placebo-controlled, single oral dose studies were performed with ODN (2-600 mg) in 44 healthy volunteers (36 men and eight postmenopausal women). Adverse experiences (AEs) with single doses of ODN were transient and mild to moderate, with the exception of one severe AE of gastroenteritis. Headache was the most frequent AE. After absorption of ODN (initial peak concentrations 4-6 h postdose), plasma concentrations exhibited a monophasic decline, with an apparent terminal half-life of ∼40-80 h. The area under the curve0-24 hours (AUC(0-24 h)), concentration at 24 hours (C(24 h)) and maximum concentration (C(max,overal)) increased in a less than dose-proportional manner from 2 to 600 mg. Administration of ODN with a high-fat meal led to ∼100% increases in AUC(0-24 h), C(max,day1), C(max,overall) and C(24 h) relative to the fasted state, while administration with a low-fat meal led to a ∼30% increase in those parameters. Reduction of biomarkers of bone resorption, the C- and N-telopeptides of cross-links of type I collagen, (CTx and NTx, respectively), was noted at 24 h for doses ≥5 mg and at 168 h postdose for ≥10 mg. In postmenopausal women administered 50 mg ODN, reductions in serum CTx of -66% and urine NTx/creatinine (uNTx/Cr) of -51% relative to placebo were observed at 24 h. At 168 h, reductions in serum CTx (-70%) and uNTx/Cr (-78%) were observed relative to baseline. Pharmacokinetic/pharmacodynamic modeling characterized the ODN concentration/uNTx/Cr relation, with a modeled EC50 value of 43.8 nM and ∼80% maximal reduction. Odanacatib was well tolerated and has a pharmacokinetic and pharmacodynamic profile suitable for once weekly dosing. © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. British Journal of

  2. Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection is Associated with Induction of Flavin-containing Monooxygenase-3 (FMO3) in Hepatocytes

    Science.gov (United States)

    Acetaminophen (APAP) pretreatment with a low hepatotoxic dose in mice results in resistance to a second, higher dose of APAP (APAP autoprotection). Recent microarray work by our group showed a drastic induction of liver flavin containing monooxygenase-3 (Fmo3) mRNA expression in...

  3. [The monophasic pattern in oral glucose tolerance test as a predictive risk factor of type 2 diabetes in obese paediatric patients].

    Science.gov (United States)

    Herrera-Martínez, Aura D; Enes, Patricia; Martín-Frías, María; Roldán, Belén; Yelmo, Rosa; Barrio, Raquel

    2017-10-01

    The onset of obesity at young ages is strongly associated with the early development of type 2diabetes (T2D). The shape of the curves of glucose and insulin curves during an oral glucose tolerance test (OGTT) could predict the risk of developing T2D. To analyse the morphology of the OGTT and determine T2D risk factors in a mainly Caucasian population of children and adolescents. Observational retrospective study including 588 patients (309 males, 279 females) with a mean age of 11.1±2years, and of whom 90.3% were Caucasian. Risk factors for T2D were compared in patients with a monophasic or biphasic pattern during the performance of an OGTT, as well as anthropometric and biochemical variables, insulin resistance, and beta-cell function. The shape of the glucose curve was monophasic in 50.2% of patients (50.8% male), biphasic in 48.5% (47.6% males), and indeterminate in 1.3%. The monophasic pattern showed lower insulin-sensitivity and worse beta-cell function. Patients with a biphasic pattern had a higher BMI, waist circumference, and blood pressure, although the results were not significant. Latin-American patients had significantly lower serum glucose levels with higher insulin levels during the OGTT. The pattern of response to an OGTT reflects different metabolic phenotypes. Paediatric patients with a biphasic pattern have lower risk-profiling for T2D. The performing of an OGTT could be useful to implement early intervention strategies in children and adolescents with obesity, in order to prevent the development of pre-diabetes or T2D. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Fasting Insulin is Better Partitioned according to Family History of Type 2 Diabetes Mellitus than Post Glucose Load Insulin of Oral Glucose Tolerance Test in Young Adults.

    Science.gov (United States)

    Francis, Saritha; Chandran, Sindhu Padinjareveedu; Nesheera, K K; Jacob, Jose

    2017-05-01

    Hyperinsulinemia is contributed by insulin resistance, hepatic insulin uptake, insulin secretion and rate of insulin degradation. Family history of type 2 diabetes mellitus has been reported to cause hyperinsulinemia. Correlation of fasting insulin with post glucose load Oral Glucose Tolerance Test (OGTT) insulin in young adults and their partitioning according to family history of type 2 diabetes. In this observational cross-sectional study, clinical evaluation and biochemical assays of insulin and diabetes related parameters, and secondary clinical influences on type 2 diabetes in volunteers were done for inclusion as participants (n=90) or their exclusion. Cut off levels of quantitative biochemical variables were fixed such that they included the effects of insulin resistance, but excluded other secondary clinical influences. Distribution was analysed by Shapiro-Wilk test; equality of variances by Levene's test; Log10 transformations for conversion of groups to Gaussian distribution and for equality of variances in the groups compared. When the groups compared had Gaussian distribution and there was equality of variance, parametric methods were used. Otherwise, non parametric methods were used. Fasting insulin was correlating significantly with 30, 60 and 120 minute OGTT insulin showing that hyperinsulinemia in the fasting state was related to hyperinsulinemia in the post glucose load states. When fasting and post glucose load OGTT insulin were partitioned into those without and with family history of type 2 diabetes, maximum difference was seen in fasting insulin (pinsulin. The 30 minute insulin could not be partitioned (p=0.574). Fasting, 60 and 120 minute OGTT insulin can be partitioned according to family history of type 2 diabetes, demonstrating stratification and heterogeneity in the insulin sample. Of these, fasting insulin was better partitioned and could be used for baseline reference interval calculations.

  5. Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

    Science.gov (United States)

    Cho, Seong Beom; Koh, InSong; Nam, Hye-Young; Jeon, Jae-Pil; Lee, Hong Kyu; Han, Bok-Ghee

    2017-01-01

    Here, we tested the performance of the mitochondrial DNA copy number (mtDNA-CN) in predicting future type 2 diabetes (n = 1108). We used the baseline clinical data (age, sex, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure) and the mtDNA-CN, hemoglobin A1c (A1C) levels and results of oral glucose tolerance test (OGTT) including fasting plasma glucose, 1-hour glucose, and 2-hour glucose levels, to predict future diabetes. We built a prediction model using the baseline data and the diabetes status at biannual follow-up of 8 years. The mean area under curve (AUC) for all follow-ups of the full model including all variables was 0.92 ± 0.04 (mean ± standard deviation), while that of the model excluding the mtDNA-CN was 0.90 ± 0.03. The sensitivity of the f4ull model was much greater than that of the model not including mtDNA-CN: the mean sensitivities of the model with and without mtDNA-CN were 0.60 ± 0.06 and 0.53 ± 0.04, respectively. We found that the mtDNA-CN of peripheral leukocytes is a biomarker that augments the predictive power for future diabetes of A1C and OGTT. We believe that these results could provide invaluable information for developing strategies for the management of diabetes. PMID:28251996

  6. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    Science.gov (United States)

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-06-21

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP.

  7. The transcriptional regulator Aire co-opts the repressive ATF7ip-MBD1 complex for induction of immune tolerance

    Science.gov (United States)

    Waterfield, Michael; Khan, Imran S.; Cortez, Jessica T.; Fan, Una; Metzger, Todd; Greer, Alexandra; Fasano, Kayla; Martinez-Llordella, Marc; Pollack, Joshua L.; Erle, David J.; Su, Maureen; Anderson, Mark S.

    2014-01-01

    The maintenance of immune tolerance requires the deletion of self-reactive T cells in the thymus. The expression of tissue-specific antigen genes (TSAs) by thymic epithelial cells is critical for this process and depends on the activity of the Autoimmune Regulator (Aire) protein, however, the molecular mechanism(s) Aire uses to target TSA gene loci are unknown. Here we identified two Aire-interacting proteins – activating transcription factor 7 interacting protein (ATF7ip) and methyl CpG binding protein 1 (MBD1) –that are required for Aire’s targeting of TSA geneloci. Moreover, Mbd1−/− mice developed pathological autoimmunity and had a defect in Aire-dependent thymic TSA gene expression underscoring the critical importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance. PMID:24464130

  8. Induction of labour at term with oral misoprostol versus a foley catheter (PROBAAT-II) : A multicentre randomised controlled non-inferiority trial

    NARCIS (Netherlands)

    Ten Eikelder, Mieke L G; Rengerink, Katrien Oude; Jozwiak, Marta; De Leeuw, Jan W.; De Graaf, Irene M.; Van Pampus, Mariëlle G.; Holswilder, Marloes; Oudijk, Martijn A.|info:eu-repo/dai/nl/246958898; Van Baaren, Gert Jan; Pernet, Paula J M; Bax, Caroline; Van Unnik, Gijs A.; Martens, Gratia; Porath, Martina; Van Vliet, Huib; Rijnders, Robbert J P; Feitsma, A. Hanneke; Roumen, Frans J M E; Van Loon, Aren J.; Versendaal, Hans; Weinans, Martin J N; Woiski, Mallory; Van Beek, Erik; Hermsen, Brenda; Mol, Ben Willem; Bloemenkamp, Kitty W M

    2016-01-01

    When pregnancy complications pose a threat to the mother or fetus or both, induction of labor is often required. Induction of labor is accomplished through a variety of methods; in pregnant women having an unfavourable cervix, cervical ripening of the cervix is accomplished through various mechanica

  9. Induction of labour with a Foley catheter or oral misoprostol at term: the PROBAAT-II study, a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Eikelder, M.L. Ten; Neervoort, F.; Oude Rengerink, K.; Jozwiak, M.; Leeuw, J.W. de; Graaf, I. de; Pampus, M.G. van; Franssen, M.; Oudijk, M.; Salm, P. van der; Woiski, M.D.; Pernet, P.J.; Feitsma, A.H.; Vliet, H. van; Porath, M.; Roumen, F.; Beek, E. van; Versendaal, H.; Heres, M.; Mol, B.W.; Bloemenkamp, K.W.

    2013-01-01

    BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin

  10. Induction of labour at term with oral misoprostol versus a foley catheter (PROBAAT-II) : A multicentre randomised controlled non-inferiority trial

    NARCIS (Netherlands)

    Ten Eikelder, Mieke L G; Rengerink, Katrien Oude; Jozwiak, Marta; De Leeuw, Jan W.; De Graaf, Irene M.; Van Pampus, Mariëlle G.; Holswilder, Marloes; Oudijk, Martijn A.; Van Baaren, Gert Jan; Pernet, Paula J M; Bax, Caroline; Van Unnik, Gijs A.; Martens, Gratia; Porath, Martina; Van Vliet, Huib; Rijnders, Robbert J P; Feitsma, A. Hanneke; Roumen, Frans J M E; Van Loon, Aren J.; Versendaal, Hans; Weinans, Martin J N; Woiski, Mallory; Van Beek, Erik; Hermsen, Brenda; Mol, Ben Willem; Bloemenkamp, Kitty W M

    2016-01-01

    When pregnancy complications pose a threat to the mother or fetus or both, induction of labor is often required. Induction of labor is accomplished through a variety of methods; in pregnant women having an unfavourable cervix, cervical ripening of the cervix is accomplished through various mechanica

  11. Induction of labour with a Foley catheter or oral misoprostol at term : the PROBAAT-II study, a multicentre randomised controlled trial

    NARCIS (Netherlands)

    ten Eikelder, Mieke L. G.; Neervoort, Femke; Rengerink, Katrien Oude; Jozwiak, Marta; de Leeuw, Jan-Willem; de Graaf, Irene; van Pampus, Maria G.; Franssen, Maureen; Oudijk, Martijn; van der Salm, Paulien; Woiski, Mallory; Pernet, Paula J. M.; Feitsma, A. Hanneke; van Vliet, Huib; Porath, Martina; Roumen, Frans; van Beek, Erik; Versendaal, Hans; Heres, Marion; Mol, Ben Willem J.; Bloemenkamp, Kitty W. M.

    2013-01-01

    Background: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin

  12. Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit.

    Science.gov (United States)

    Sun, J-B; Czerkinsky, C; Holmgren, J

    2010-01-01

    Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non-toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof-of-concept clinical trial in patients with Behcet's disease, this was extended with highly promising results to prevent relapse of autoimmune uveitis. Tolerization by mucosal Ag/CTB administration results in a strong increase in Ag-specific regulatory CD4(+) T cells, apparently via two separate pathways: one using B cells as APCs and leading to a strong expansion of Foxp3(+) Treg cells which can both suppress and mediate apoptotic depletion of effector T cells, and one being B cell-independent and associated with development of Foxp3(-) regulatory T cells that express membrane latency-associated peptide and transforming growth factor (TGF-beta) and/or IL-10. The ability of CTB to dramatically increase mucosal Ag uptake and presentation by different APCs through binding to GM1 ganglioside (which makes most B cells effective APCs irrespective of their Ag specificity), together with CTB-mediated stimulation of TGF-beta and IL-10 production and inhibition of IL-6 formation may explain the dramatic potentiation of oral tolerance by mucosal Ags presented with CTB.

  13. The CD28/CTLA-4-B7 signaling pathway is involved in both allergic sensitization and tolerance induction to orally administered peanut proteins.

    NARCIS (Netherlands)

    Wijk, F. van; Nierkens, S.; Jong, W. de; Wehrens, E.J.; Boon, L.; Kooten, P. van; Knippels, L.M.; Pieters, R.

    2007-01-01

    Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one

  14. Increased intake of vegetable oil rich in n-6 PUFA enhances allergic symptoms and prevents oral tolerance induction in whey-allergic mice

    NARCIS (Netherlands)

    van den Elsen, Lieke W J; van Esch, Betty C A M; Dingjan, Gemma M; Hofman, Gerard A; Garssen, Johan; Willemsen, Linette E M

    2015-01-01

    Increased intake of vegetable oils rich in n-6 PUFA, including soyabean oil, has been associated with an increase in allergic disease. The present study aimed to determine the effect of an increasing dose of dietary vegetable oil on allergic outcomes in mice. To study this, mice received a 7 v. 10 %

  15. Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

    Directory of Open Access Journals (Sweden)

    Silke A Herzberg-Schäfer

    Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

  16. Risk factor screening to identify women requiring oral glucose tolerance testing to diagnose gestational diabetes: A systematic review and meta-analysis and analysis of two pregnancy cohorts.

    Science.gov (United States)

    Farrar, Diane; Simmonds, Mark; Bryant, Maria; Lawlor, Debbie A; Dunne, Fidelma; Tuffnell, Derek; Sheldon, Trevor A

    2017-01-01

    Easily identifiable risk factors including: obesity and ethnicity at high risk of diabetes are commonly used to indicate which women should be offered the oral glucose tolerance test (OGTT) to diagnose gestational diabetes (GDM). Evidence regarding these risk factors is limited however. We conducted a systematic review (SR) and meta-analysis and individual participant data (IPD) analysis to evaluate the performance of risk factors in identifying women with GDM. We searched MEDLINE, Medline in Process, Embase, Maternity and Infant Care and the Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2016 and conducted additional reference checking. We included observational, cohort, case-control and cross-sectional studies reporting the performance characteristics of risk factors used to identify women at high risk of GDM. We had access to IPD from the Born in Bradford and Atlantic Diabetes in Pregnancy cohorts, all pregnant women in the two cohorts with data on risk factors and OGTT results were included. Twenty nine published studies with 211,698 women for the SR and a further 14,103 women from two birth cohorts (Born in Bradford and the Atlantic Diabetes in Pregnancy study) for the IPD analysis were included. Six studies assessed the screening performance of guidelines; six examined combinations of risk factors; eight evaluated the number of risk factors and nine examined prediction models or scores. Meta-analysis using data from published studies suggests that irrespective of the method used, risk factors do not identify women with GDM well. Using IPD and combining risk factors to produce the highest sensitivities, results in low specificities (and so higher false positives). Strategies that use the risk factors of age (>25 or >30) and BMI (>25 or 30) perform as well as other strategies with additional risk factors included. Risk factor screening methods are poor predictors of which pregnant women will be diagnosed with GDM. A simple approach of

  17. Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II) : A multicentre randomised controlled non-inferiority trial

    NARCIS (Netherlands)

    ten Eikelder, Mieke L G; Oude Rengerink, Katrien; Jozwiak, Marta; de Leeuw, Jan W.; de Graaf, Irene M.; van Pampus, Mariëlle G.; Holswilder, Marloes; Oudijk, Martijn A.; van Baaren, Gert Jan; Pernet, Paula J M; Bax, Caroline; van Unnik, Gijs A.; Martens, Gratia; Porath, Martina; van Vliet, Huib; Rijnders, Robbert J P; Feitsma, A. Hanneke; Roumen, Frans J M E; van Loon, Aren J.; Versendaal, Hans; Weinans, Martin J N; Woiski, Mallory; van Beek, Erik; Hermsen, Brenda; Mol, Ben Willem; Bloemenkamp, Kitty W M

    2016-01-01

    BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral mis

  18. Enhanced formation of aerenchyma and induction of a barrier to radial oxygen loss in adventitious roots of Zea nicaraguensis contribute to its waterlogging tolerance as compared with maize (Zea mays ssp. mays).

    Science.gov (United States)

    Abiko, Tomomi; Kotula, Lukasz; Shiono, Katsuhiro; Malik, Al Imran; Colmer, Timothy David; Nakazono, Mikio

    2012-09-01

    Enhancement of oxygen transport from shoot to root tip by the formation of aerenchyma and also a barrier to radial oxygen loss (ROL) in roots is common in waterlogging-tolerant plants. Zea nicaraguensis (teosinte), a wild relative of maize (Zea mays ssp. mays), grows in waterlogged soils. We investigated the formation of aerenchyma and ROL barrier induction in roots of Z. nicaraguensis, in comparison with roots of maize (inbred line Mi29), in a pot soil system and in hydroponics. Furthermore, depositions of suberin in the exodermis/hypodermis and lignin in the epidermis of adventitious roots of Z. nicaraguensis and maize grown in aerated or stagnant deoxygenated nutrient solution were studied. Growth of maize was more adversely affected by low oxygen in the root zone (waterlogged soil or stagnant deoxygenated nutrient solution) compared with Z. nicaraguensis. In stagnant deoxygenated solution, Z. nicaraguensis was superior to maize in transporting oxygen from shoot base to root tip due to formation of larger aerenchyma and a stronger barrier to ROL in adventitious roots. The relationships between the ROL barrier formation and suberin and lignin depositions in roots are discussed. The ROL barrier, in addition to aerenchyma, would contribute to the waterlogging tolerance of Z. nicaraguensis.

  19. Tolerating Zero Tolerance?

    Science.gov (United States)

    Moore, Brian N.

    2010-01-01

    The concept of zero tolerance dates back to the mid-1990s when New Jersey was creating laws to address nuisance crimes in communities. The main goal of these neighborhood crime policies was to have zero tolerance for petty crime such as graffiti or littering so as to keep more serious crimes from occurring. Next came the war on drugs. In federal…

  20. IL-33 Enhances Host Tolerance to Candida albicans Kidney Infections through Induction of IL-13 Production by CD4+ T Cells.

    Science.gov (United States)

    Tran, Vuvi G; Kim, Hye J; Kim, Juyang; Kang, Sang W; Moon, U J; Cho, Hong R; Kwon, Byungsuk

    2015-05-15

    Susceptibility to systemic Candida albicans infection is determined by immune resistance, as well as by the ability to control Candida-induced immunopathologies. We showed previously that exogenous IL-33 can increase resistance to peritoneal C. albicans infection by regulating multiple steps of the neutrophil anti-Candida response. In this study, using a mouse model of systemic candidiasis, we observed that IL-33 administration limited fungal burden and inflammation and increased survival. In kidneys, IL-33 seemed to directly act on neutrophils and CD4(+) T cells: IL-33 administration enhanced fungal clearance by increasing neutrophil phagocytic activity without which Candida proliferation was uncontrollable. In contrast, IL-33 stimulated CD4(+) T cells to produce IL-13, which, in turn, drove the polarization of macrophages toward the M2 type. Furthermore, the absence of IL-13 abolished IL-33-mediated polarization of M2 macrophages and renal functional recovery. In addition, IL-33 and IL-13 acted synergistically to increase M2 macrophage polarization and its phagocytic activity. Overall, this study identifies IL-33 as a cytokine that is able to induce resistance and tolerance and suggests that targeting resistance and tolerance simultaneously with therapeutic IL-33 may benefit patients with systemic candidiasis.

  1. A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms desogestrel, with respect to efficacy, cycle control and tolerance.

    Science.gov (United States)

    Endrikat, J; Jaques, M A; Mayerhofer, M; Pelissier, C; Müller, U; Düsterberg, B

    1995-10-01

    The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p=0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

  2. A importância do teste de tolerância à glicose oral no diagnóstico da intolerância à glicose e diabetes mellitus do tipo 2 em mulheres com síndrome dos ovários policísticos The importance of oral glucose tolerance test in diagnosis of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Pontes

    2012-03-01

    Full Text Available OBJETIVO: Avaliar a importância do teste de tolerância à glicose oral (TTGO no diagnóstico da intolerância à glicose (IG e diabetes mellitus do tipo 2 (DM-2 em mulheres com SOP. MÉTODOS: Estudo retrospectivo em que foram incluídas 247 pacientes portadoras de SOP, selecionadas de forma aleatória. O diagnóstico de IG foi obtido por meio do TTGO de duas horas com 75 gramas de glicose de acordo com os critérios do World Health Organization (WHO (IG: glicemia plasmática aos 120 minutos >140 mg/dL e 200 mg/dL quanto pela glicemia de jejum segundo os critérios da American Diabetes Association (glicemia de jejum alterada: glicemia plasmática >100 e 126 mg/dL. Para comparar o TTGO com a glicemia de jejum foi aplicado o modelo de regressão logística para medidas repetidas. Para a análise das características clínicas e bioquímicas das pacientes com e sem IG e/ou DM-2 foi utilizada a ANOVA seguida do teste de Tukey. O valor pPURPOSE: To evaluate the importance of the oral glucose tolerance test for the diagnosis of glucose intolerance (GI and type 2 diabetes mellitus (DM-2 in women with PCOS. METHODS: A retrospective study was conducted on 247 patients with PCOS selected at random. The diagnosis of GI was obtained from the two-hour oral glucose tolerance test with 75 g of glucose according to the criteria of the World Health Organization (WHO (GI: 120 minutes for plasma glucose >140 mg/dL and 200 mg/dL and fasting glucose using the criteria of the American Diabetes Association (impaired fasting glucose: fasting plasma glucose >100 and 126 mg/dL. A logistic regression model for repeated measures was applied to compare the oral glucose tolerance test with fasting plasma glucose. ANOVA followed by the Tukey test was used for the analysis of the clinical and biochemical characteristics of patients with and without GI and/or DM-2. A p<0.05 was considered statistically significant. RESULTS: PCOS patients had a mean age of 24.8±6.3, and body

  3. Low-dose oral tolerance due to antigen in the diet suppresses differentially the cholera toxin-adjuvantized IgE, IgA and IgG response

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Kjær, Tanja; Frøkiær, Hanne

    2003-01-01

    Background: Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Priorly established oral tolerance due to antigen...... soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined. Results: The anti......-KSTI IgE and IgA responses in the F0 mice were substantially suppressed, while the IgG1 and IgG2a responses were not suppressed after five oral immunizations. The response suppression tended to decline with increasing numbers of immunizations suggesting that the suppression could be overcome by multiple...

  4. Direct Torque and Fault Tolerant Control for Six-phase Induction Motor%六相感应电机直接转矩及容错控制

    Institute of Scientific and Technical Information of China (English)

    耿乙文; 鲍宇; 王昊; 马鸿宇

    2016-01-01

    The problem of large torque ripples exists in conventional direct torque control (DTC). Based on the consideration of the six-phase induction motor with its own characteristics and analysis of the mathematical model, the paper proposed a six-phase induction motor direct torque control method. Firstly, the mathematical model of motors with normal and stator winding open-circuited conditions was built and analyzed respectively. Furthermore, formulation of a space vector pulse width modulation (SVPWM) provides a method to reduce stator current harmonics of the motor. Analysis of torque and flux provides a theoretical basis for the direct torque control. Finally, using the fuzzy reasoning and changing the duty ratio of the vector action time method, the inverter can output any angle and amplitude of the voltage vector. Experimental results show that the proposed strategy is able to reduce torque ripples and can improve current waveforms, and the torque dynamic response of the system is fast.%针对传统直接转矩控制转矩脉动大的问题,在考虑六相感应电机自身特点及分析其缺相数学模型的基础上,提出了一种六相感应电机直接转矩及容错控制方法。首先,建立和分析电机正常及缺相时的数学模型,并确定空间矢量脉宽调制(space vector pulse width modulation,SVPWM)方案以减小电机定子电流谐波含量;然后,通过对电机转矩和磁链进行分析,为直接转矩控制提供理论依据;在此基础上,利用模糊推理和改变矢量作用时间占空比的方法,使得逆变器可以输出任意角度和幅值的电压矢量。实验结果表明,该控制方案下电机转矩响应迅速,并能很好地改善电机转矩脉动和定子电流波形。

  5. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  6. Induction time of Fe-SOD synthesis and activity determine different tolerance of two Desmodesmus (green algae) strains to chloridazon: a study with synchronized cultures.

    Science.gov (United States)

    Pokora, Wojciech; Tukaj, Zbigniew

    2013-09-01

    Cells of two Desmodesmus armatus strains (276-4a and 276-4d) grown asynchronously in batch cultures after 24-h treatment revealed different tolerance to chloridazon (photosynthetic herbicide) applied at a concentration of 3.45 mg L(-1). To find time- and cell cycle-dependent biochemical reasons leading to such a difference, a population of young autospores of both strains synchronized by a light/dark (14/10) regime were exposed to chloridazon at the initiation of the light period. Chloridazon reduced the growth and number of divisions of cell strain 276-4d. In consequence, at the end of the dark phase the number of released autospores was reduced by 50% compared with the control. In contrast, the growth and reproductive processes of cell strains 276-4a was unaffected. Moreover, chloridazon treatment speeded up cell development, as a result of which the release of autospores took this process observed in the control cells over. There is a relationship between photosynthetic activity response to chloridazon and time-dependent changes in Fe-SOD content and activity. The energy trapped in the reaction centre (RC) was similar in both strains, but the amount of energy absorbed by RCs was twice as high in strain 276-4d as in 276-4a. In consequence, non-photochemical energy dissipation occurring in the cells of 276-4d strain far exceed the value obtained for 276-4a strain. The control cells of both strains differed significantly in the content of FSD 1 and FSD 2 proteins, whereas the differences in Fe-SOD isoforms activities were slight. The 8-fold increase in SOD content in CHD treated cells of strain 276-4a was associated with the transience of photosynthetic efficiency impairment. In CHD treated cells of strain 276-4d, neither activity of Fe-SOD nor FSDs protein content was instantly affected. Different response of developing cells of two Desmodesmus strains to CHD is influenced by the inherent features of cells; the short time required to induce stress adaptive

  7. Assessment of glucose metabolism in polycystic ovary syndrome: HbA1c or fasting glucose compared with the oral glucose tolerance test as a screening method.

    Science.gov (United States)

    Lerchbaum, E; Schwetz, V; Giuliani, A; Obermayer-Pietsch, B

    2013-09-01

    Are HbA1c and fasting glucose (FG) useful in predicting the presence of prediabetes and type 2 diabetes (T2DM) in a large cohort of women with polycystic ovary syndrome (PCOS)? HbA1c and FG are not suitable as screening tools for prediabetes in a large cohort of PCOS women but do show a good level of agreement with T2DM. Women with PCOS have an increased risk of prediabetes and T2DM. As performing an oral glucose tolerance test (OGTT) is time consuming, HbA1c and FG have been suggested as screening tools for prediabetes and T2DM. This was a cross-sectional study of 671 women with PCOS conducted from 2006 to 2012. The study was carried out at the endocrinological outpatient department of the Medical University of Graz, Austria. We performed 75 g 2-h OGTTs and measured HbA1c in 671 women with PCOS aged 16-45 years with a median BMI of 24.2 (21.3-30.1) kg/m². PCOS was defined according to the Rotterdam criteria. Prediabetes (FG 100-125 mg/dl and/or 2-h glucose 140-199 mg/dl and/or HbA1c 5.7-6.4%) and T2DM (FG ≥ 126 mg/dl and/or 2-h glucose ≥200 mg/dl and/or HbA1c ≥ 6.5%) were diagnosed according to the American Diabetes Association (ADA) criteria. Levels of agreement between different definitions were analyzed using κ-index. According to the ADA criteria, we found prediabetes and T2DM in 12.8% (n = 76) and 1.5% (n = 9) of PCOS women, respectively. When using elevated HbA1c (5.7-6.4%) for defining prediabetes, 19 (3.2%) of all PCOS women had prediabetes with a κ-index of 0.36. When using elevated FG (100-125 mg/dl) for defining prediabetes, 31 (5.2%) of all the PCOS women were diagnosed with prediabetes with a κ-index of 0.05. Further, elevated HbA1c (≥6.5% defining T2DM) was found in six (0.9%) PCOS women (κ-index 0.80), and elevated FG (≥126 mg/dl diagnosing T2DM) was found in seven PCOS women (1%; κ-index 0.82). Our results are limited to an Austrian cohort of PCOS women diagnosed by Rotterdam criteria with a median BMI in the normal weight range

  8. Accumulation and tolerance to cadmium heavy metal ions and induction of 14-3-3 gene expression in response to cadmium exposure in Coprinus atramentarius.

    Science.gov (United States)

    Xie, Chengjian; Hu, Liujie; Yang, Yongzhu; Liao, Dunxiu; Yang, Xingyong

    2017-03-01

    Cadmium (Cd), one of the most toxic heavy-metal pollutants, has a strong and irreversible tendency to accumulate. Bioremediation is a promising technology to remedy and control heavy metal pollutants because of its low cost and ability to recycle heavy metals. Coprinus atramentarius is recognized as being able to accumulate heavy metal ions. In this work, C. atramentarius is cultivated on a solid medium containing Cd(2+) ions to analyze its ability to tolerate different concentrations of the heavy metal ion. It is found that the growth of C. atramentarius is not significantly inhibited when the concentration of Cd(2+) is less than 0.6mgL(-1). The accumulation capacity of C. atramentarius at different Cd(2+) concentrations also was determined. The results show that 76% of the Cd(2+) present can be accumulated even when the concentration of the Cd(2+) is 1mgL(-1). The different proteins of C. atramentarius exposed to Cd(2+) were further analyzed using gel electrophoresis. A 14-3-3 protein was identified and shown to be significantly up-regulated. In a further study, a full-length 14-3-3 gene was cloned containing a 759bp open reading frame encoding a polypeptide consisting of 252 amino acids and 3 introns. The gene expression work also showed that the 14-3-3 was significantly induced, and showed coordinated patterns of expression, with Cd(2+) exposure.

  9. Induction of xenogeneic islet transplantation tolerance by simultaneously blocking CD28-B7 and OX40-OX40L co-stimulatory pathways

    Institute of Scientific and Technical Information of China (English)

    WANG; Guangming; FENG; Yougang; HAO; Jie; LI; Ailing; GAO

    2005-01-01

    It has been demonstrated that prolonged graft survival can be achieved through inhibiting the activation of T cells, and addition of soluble CTLA4Ig and OX40Ig proteins to mixed lymphocyte reactions can effectively inhibit T cell proliferation. To explore the potential of this type of treatment in xenotransplantation, we infected streptozotocin-induced diabetic BalB/c mice (H-2d) (200 mg/kg, IV) with 5×108 pfu AdCTLA4Ig-IRES-OX40Ig on day 1 before islets transplantation through the tail vein. The results showed that this treatment prolonged the islet xenografts survival significantly. The reaction to exogenous glucose stimulation was normal and the cytokine secretion of the type Th1 cells was inhibited. The AdCTLA4Ig-IRES-OX40Ig-mediated treatment effectively induced the T cells into anergy and the Th1/Th2 cells into deviation. These results strongly supported the therapeutic potential of blockade of costimulation by AdCTLA4Ig-IRES-OX40Ig genes transfer in inducing the organ transplantation tolerance.

  10. The Leu7Pro polymorphism of preproNPY is associated with decreased insulin secretion, delayed ghrelin suppression, and increased cardiovascular responsiveness to norepinephrine during oral glucose tolerance test.

    Science.gov (United States)

    Jaakkola, Ulriikka; Kuusela, Tom; Jartti, Tuomas; Pesonen, Ullamari; Koulu, Markku; Vahlberg, Tero; Kallio, Jaana

    2005-06-01

    Neuropeptide Y (NPY) plays a role in angiogenesis, cardiovascular regulation, and hormone secretion. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY is associated with vascular diseases and has an impact on hormone levels in healthy subjects. The current study investigated the role of the Leu7Pro polymorphism in metabolic and cardiovascular autonomic regulation. A 5-h oral glucose tolerance test was performed on 27 healthy volunteers representing two preproNPY genotypes (Leu7/Pro7 and Leu7/Leu7) matched for age, sex, body mass index and physical activity. Simultaneously we performed cardiovascular autonomic function tests and plasma measurements of sympathetic transmitters, glucose, insulin, and ghrelin. The subjects with Leu7/Pro7 genotype had decreased plasma NPY, norepinephrine (NE), and insulin concentrations and insulin to glucose ratios. The suppression of ghrelin concentrations after glucose ingestion was delayed in these subjects. They also had increased heart rate variability indices and baroreflex sensitivity. However, they displayed significant negative association of NE concentration with variability of low-frequency R-R-intervals and with baroreflex sensitivity. The Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test. The increased responsiveness of autonomic functions to NE associated with the polymorphism may be connected to increased cardiovascular vulnerability.

  11. Efficiency of systemic versus intralesional bone marrow-derived stem cells in regeneration of oral mucosa after induction of formocresol induced ulcers in dogs.

    Science.gov (United States)

    Aly, Lobna A; El-Menoufy, Hala; Sadeq, Hesham S; Ragae, Alyaa; Sabry, Dina

    2014-03-01

    Bone marrow mesenchymal stem cells (BMSCs) are the key to regenerative wound healing. MSCs have spatial memory and respond to local environment. The goal of this study was to evaluate the use of systemic and intralesional transplantation of BMSCs for regeneration of oral mucosa in an in vivo dog model. Transplantation of undifferentiated green fluorescent protein (GFP)-labeled autologous BMSCs systemically, submucosally or vehicle (saline) was injected around the chemically induced oral ulcer in each group of 18 adult dogs. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) and collagen genes was detected in biopsies from all ulcers. One way ANOVA was used to compare between means of the three groups. Results were considered significant at P < 0.05. Flow cytometric analysis of the MSCs at the passage 3 showed that these cells were negative for CD45 (2.39%). They expressed high levels of CD29 (98.34%). Frozen fluorescence microscopy of sections of the cell-treated oral tissue of all groups indicated that the GFP-transduced implanted cells were integrated within the transplanted tissues. The treatment resulted in dramatic wound edge activation and resurfacing of oral mucosa wound. Our results revealed that BMSCs may be labeled with (GFP), in order to know the distribution of these cells after administration, and suggest that intralesional administration is an appropriate procedure to achieve acceptable regeneration of the previously injured oral mucosa more than systemic route.

  12. Evaluation of an intensive desensitisation, oral tolerance therapy and hunger provocation program for children who have had prolonged periods of tube feeds

    OpenAIRE

    Harding, C.; Faiman, A.; Wright, J

    2010-01-01

    Background: Some children with early feeding difficulties may require nasogastric, (NG) tube feeding or insertion of a percutaneous endoscopic gastrostomy, (PEG) from a young age. A small cohort of these children can develop severe oral aversions that can delay the re-introduction of oral feeding. Multi-disciplinary approaches that provide an intensive approach are deemed the most effective method of intervention to reduce NG and PEG dependency. Method: Two children and their parents rec...

  13. Light acclimation of shade-tolerant and light-resistant Tradescantia species: induction of chlorophyll a fluorescence and P700 photooxidation, expression of PsbS and Lhcb1 proteins.

    Science.gov (United States)

    Mishanin, Vladimir I; Trubitsin, Boris V; Benkov, Michael A; Minin, Andrei A; Tikhonov, Alexander N

    2016-12-01

    In this work, we have compared photosynthetic performance and expression of the PsbS and Lhcb1 proteins in two contrast ecotypes of Tradescantia species, T. fluminensis (shade-tolerant) and T. sillamontana (light-resistant), grown at two intensities of light: 50-125 μmol photons m(-2) s(-1) (low light, LL) and 875-1000 μmol photons m(-2) s(-1) (high light, HL). Using the EPR method for measuring the P700 content, we have found that LL-grown plants of both species have higher (by a factor of ≈1.7-1.8) contents of PSI per fresh weight unit as compared to HL-grown plants. Acclimation of plants to LL or HL irradiation also influences the Chl(a + b) level and expression of the PsbS and Lhcb1 proteins. Immunoblotting analysis showed that acclimation to HL stimulates (by a factor of ≈1.7-1.8) the level of PsbS related to the total number of P700 centers. In light-resistant species T. sillamontana, the ratio PsbS/P700 is about 2-times higher than in shade-tolerant species T. fluminensis grown under the same conditions. This should enhance the capacity of their leaves for protection against the light stress. In agreement with these observations, the capacity of leaves for NPQ induction was enhanced during plant acclimation to HL. Kinetic studies of P700 photooxidation and light-induced changes in the yield of Chl a fluorescence also revealed that the short-term regulation of electron transport processes in chloroplasts, which manifested themselves in the kinetics of [Formula: see text] induction and the rate of Chl a fluorescence quenching, occurred more rapidly in HL-grown plants than in LL-grown plants. Thus, both factors, enhanced expression of PsbS and more rapid response of the photosynthetic electron transport chain to dark-to-light transitions should increase the capacity of HL-grown plants for their resistance to rapid fluctuations of solar light.

  14. Differential gene expression and mitotic cell analysis of the drought tolerant soybean (Glycine max L. Merrill Fabales, Fabaceae cultivar MG/BR46 (Conquista under two water deficit induction systems

    Directory of Open Access Journals (Sweden)

    Polyana K. Martins

    2008-01-01

    Full Text Available Drought cause serious yield losses in soybean (Glycine max, roots being the first plant organ to detect the water-stress signals triggering defense mechanisms. We used two drought induction systems to identify genes differentially expressed in the roots of the drought-tolerant soybean cultivar MG/BR46 (Conquista and characterize their expression levels during water deficit. Soybean plants grown in nutrient solution hydroponically and in sand-pots were submitted to water stress and gene expression analysis was conducted using the differential display (DD and real time polymerase chain reaction (PCR techniques. Three differentially expressed mRNA transcripts showed homology to the Antirrhinum majus basic helix-loop-helix transcription factor bHLH, the Arabidopsis thaliana phosphatidylinositol transfer protein PITP and the auxin-independent growth regulator 1 (axi 1. The hydroponic experiments showed that after 100 min outside the nutrient solution photosynthesis completely stopped, stomata closed and leaf temperature rose. Both stress induction treatments produced significant decrease in the mitotic indices of root cells. Axi 1, PITP and bHLH were not only differentially expressed during dehydration in the hydroponics experiments but also during induced drought in the pot experiments. Although, there were differences between the two sets of experiments in the time at which up or down regulation occurred, the expression pattern of all three transcripts was related. Similar gene expression and cytological analysis results occurred in both systems, suggesting that hydroponics could be used to simulate drought detection by roots growing in soil and thus facilitate rapid and easy root sampling.

  15. Influence of mycophenolate mofetil (MMF) upon the maturation and allo-stimulatory activity of cultured progenitors of dendritic cells and the effects on the tolerance induction in allograft recipients

    Institute of Scientific and Technical Information of China (English)

    CONGHUIHAN; YUXINWANG; QINGLIANG; MINGZHANG; YINGWANG; MINGYIN; ZHILIANMING; KELIZHENG

    2005-01-01

    To investigate the influence of mycophenolate mofetil (MMF) upon the maturation and the allo-stimulatory activity of cultured progenitors of dendritic cells (DCp), and to evaluate the effects of the pre-treated dentritic cells of recipients with MMF on the tolerance induction as well as its possible mechanism, GM-CSF and MMF were added to the in vitro cultured progenitor cells, and the immuno-phenotypical analysis was performed by means of flow cytometry. The secretion of IL-12 was detected by ELISA and the stimulatory activities of DCp on allogeneic T cells were observed by mixed lymphocyte reaction.Twenty-four C57BL/6 mice were divided into 3 groups (each with 8 mice), in which group A of mice accepted allografts of heart from BALB/c mice, group B of mice had received untreated DCp from donors of BALB/c mice 7 days before transplantation, and C57BL/6 mice in group C were treated by injection with MMF-treated allografts of heart from BALB/c mice 7 days before transplantation. The survival times of allografts and the changes of the cytokine levels in sere of the recipient mice were observed after transplantation. The experimental results showed that MMF could significantly inhibit the expressions of the costimulatory molecules CD80 and CD86 on DCs and the secretion of IL-12 and the allo-stimulatory activities of DCs were also markedly inhibited. The survival times of allografts in group B of mice were longer than those in group A, while the group C showed the longest survival times of allografts, with a marked reduction in the production of the Thl type cytokines. It is evident that MMF has a suppressive effect on the maturation and allo-stimulatory activities of the cultured dendritic cell progenitors, thus leading to a donor specific tolerance in heart-transplanted recipients.

  16. Research Progress of 1-hour Hyperglycemia after Oral Glucose Tolerance Test%口服葡萄糖耐量试验后1h高血糖的研究进展

    Institute of Scientific and Technical Information of China (English)

    钟志标

    2012-01-01

    1 -hour hyperglycemia during oral glucose tolerance test is a transitional state of abnormal glucose regulation from normal glucose tolerance to type 2 diabetes mellitus. It is an independent risk factor for both type 2 diabetes mellitus and cardiovascular disease. Compared with normal glucose tolerance persons,they have a decreased (3 cell function and higher probability of the conversion to impaired glucose regulation or type 2 diabetes mellitus. Weight control,reasonable exercise and drugs such as biguanides can improve insulin pcell function, thus decrease serum glucose level.%口服葡萄糖耐量试验后1h高血糖是正常糖耐量过渡到2型糖尿病的异常糖代谢状态,它是2型糖尿病和心血管疾病的独立危险因素,与正常血糖人群相比,其胰岛β细胞功能已经降低,更容易发展成为葡萄糖调节受损或2型糖尿病的状态.控制体质量,适当的运动,服用双胍类均可改善胰岛β细胞功能,从而降低血糖水平.

  17. Prospects and strategies for clinical tolerance.

    Science.gov (United States)

    Monaco, A P

    2004-01-01

    The morbidity and mortality associated with chronic immunosuppression provide a strong motivation for development of clinical tolerance. This paper discusses the definition(s) of clinical (operational) tolerance, the role of chimerism in experimental and clinical tolerance, and the special role of bone marrow in tolerance induction. The states of microchimerism and macrochimerism are defined and related to certain clinical observations in solid organ transplantation. Current clinical strategies already being tested in the clinic are briefly reviewed. Certain principles for induction of clinical (operational) tolerance are elaborated.

  18. Globular Adiponectin Causes Tolerance to LPS-Induced TNF-α Expression via Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis.

    Science.gov (United States)

    Pun, Nirmala Tilija; Subedi, Amit; Kim, Mi Jin; Park, Pil-Hoon

    2015-01-01

    Adiponectin, an adipokine predominantly produced from adipose tissue, exhibited potent anti-inflammatory properties. In particular, it inhibits production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In the present study, we investigated the role of autophagy induction in the suppression of Lipopolysaccharide (LPS) -induced TNF-α expression by globular adiponectin (gAcrp) and its potential mechanisms. Herein, we found that gAcrp treatment increased expression of genes related with autophagy, including Atg5 and microtubule-associated protein light chain (LC3B), induced autophagosome formation and autophagy flux in RAW 264.7 macrophages. Similar results were observed in primary macrophages isolated peritoneum of mice. Interestingly, inhibition of autophagy by pretreatment with Bafilomycin A1 or knocking down of LC3B gene restored suppression of TNF-α expression, tumor necrosis factor receptor- associated factor 6 (TRAF6) expression and p38MAPK phosphorylation by gAcrp, implying a critical role of autophagy induction in the development of tolerance to LPS-induced TNF-α expression by gAcrp. We also found that knocking-down of FoxO3A, a forkhead box O member of transcription factor, blocked gAcrp-induced expression of LC3II and Atg5. Moreover, gene silencing of Silent information regulator 1 (SIRT1) blocked both gAcrp-induced nuclear translocation of FoxO3A and LC3II expression. Finally, pretreatment with ROS inhibitors, prevented gAcrp-induced SIRT1 expression and further generated inhibitory effects on gAcrp-induced autophagy, indicating a role of ROS production in gAcrp-induced SIRT1 expression and subsequent autophagy induction. Taken together, these findings indicate that globular adiponectin suppresses LPS-induced TNF-α expression, at least in part, via autophagy activation. Furthermore, SIRT1-FoxO3A

  19. Phytohormones and induction of plant-stress tolerance and defense genes by seed and foliar inoculation with Azospirillum brasilense cells and metabolites promote maize growth.

    Science.gov (United States)

    Fukami, Josiane; Ollero, Francisco Javier; Megías, Manuel; Hungria, Mariangela

    2017-12-01

    seeds or by leaf spray, as well as of leaf spraying of Azospirillum metabolites, are strongly correlated with the synthesis of phytohormones and by eliciting genes related to plant-stress tolerance and defense against pathogens.

  20. 水杨酸在诱导番茄抗冷性中的作用%Effects of salicylic acid on induction of chilling tolerance in tomato seedlings

    Institute of Scientific and Technical Information of China (English)

    马占青; 李新旭; 孙国钧; 任红旭

    2013-01-01

    以番茄为试验材料,探讨了叶面喷施水杨酸对于番茄幼苗抗低温能力的影响.实验结果表明番茄叶片中的SA在常温下主要以结合态形式存在.低温下SA质量分数大幅上升,而造成其上升的主要原因是游离态SA的大量积累.对番茄叶面喷施不同浓度SA,24 h后番茄叶片中游离态SA和结合态SA均大量积累,并且积累程度与喷施浓度呈显著正相关.低温下番茄叶片的抗氧化防御系统被明显激发,但并不足以减缓低温胁迫对植物所造成的氧化损伤.对番茄幼苗进行不同浓度的SA预处理,发现0.5 mmol/L SA能够显著提高其抗冷性.0.5 mmol/L SA预处理24 h后,低温下番茄叶片的相对电导率、MDA浓度较对照明显降低,而H2O2质量分数以及CAT, POD, APX, GR的活性则显著上升,叶片内c(AsA)/c(DHA)与c(GSH)/c(GSSG)维持在相对稳定的水平.因此,我们推测对番茄幼苗进行适宜浓度的SA预处理能够使其叶片中的SA质量分数上升至一定程度,从而诱导H2O2的适量积累,上调植物的抗氧化能力,使植物细胞在低温下维持相对稳定的氧化还原状态,从而缓解了低温对植物所造成的氧化损伤,提高了其抗冷性.%The effects of exogenous salicylic acid (SA) on inducing the chilling tolerance of tomato seedlings (Solanum lycopersicum ) was investigated and the results showed that SA mainly existed in conjugated form in tomato leaves under normal conditions. Under chilling conditions, tomato leaves contained relatively high SA levels, which should be attributed to the large accumulation of free SA. After foliar application of different concentrations of SA for 24 h, both free SA and conjugated SA largely accumulated, and the accumulation magnitude was positively correlated with the concentration of SA applied. Although the antioxidant capacity of tomato leaves was substantially enhanced under chilling conditions, the oxidative injury caused by low tempera-ture was not

  1. Cell cycle arrest and mechanism of apoptosis induction in H400 oral cancer cells in response to Damnacanthal and Nordamnacanthal isolated from Morinda citrifolia.

    Science.gov (United States)

    Shaghayegh, Gohar; Alabsi, Aied M; Ali-Saeed, Rola; Ali, Abdul Manaf; Vincent-Chong, Vui King; Zain, Rosnah Binti

    2016-10-01

    Oral cancer is the eleventh most prevalent cancer worldwide. The most prevalent oral cancer is oral squamous cell carcinoma (OSCC). Damnacanthal (DAM) and nordamnacanthal (NDAM), the anthraquinone compounds, are isolated from the root of Morinda citrifolia L. (Noni), which has been used for the treatment of several chronic diseases including cancer. The objectives of this study were to evaluate the cytotoxicity, cell death mode, cell cycle, and the molecular mechanism of apoptosis induced by DAM and NDAM on OSCC. The cytotoxic effects of these compounds against OSCC cell lines were determined by MTT assay. The cell death mode was analysed by DNA laddering and FITC-annexin V/PI flow cytometric assays. In addition, the mechanism of apoptosis induced by DAM and NDAM was detected using mitochondrial membrane potential, Cytochrome c, and caspases assays. Finally, the effect of DAM and NDAM on cell cycle phase distribution of OSCC cells was detected by flow cytometry. In the present study, DAM and NDAM showed cytotoxicity towards OSCC cell lines and the maximum growth inhibition for both compounds was observed in H400 cells with IC50 value of 1.9 and 6.8 μg/ml, respectively, after 72 h treatment. The results also demonstrated the inhibition of H400 OSCC cells proliferation, internucleosomal cleavage of DNA, activation of intrinsic apoptosis pathway, and cell cycle arrest caused by DAM and NDAM. Therefore, these findings suggest that DAM and NDAM can be potentially used as antitumor agents for oral cancer therapy.

  2. Induction of protective immune responses against the challenge of Actinobacillus pleuropneumoniae by the oral administration of transgenic tobacco plant expressing ApxIIA toxin from the bacteria.

    Science.gov (United States)

    Lee, Kyung-Yeol; Kim, Dong-Heon; Kang, Tae-Jin; Kim, Ju; Chung, Gook-Hyun; Yoo, Han-Sang; Arntzen, Charles J; Yang, Moon-Sik; Jang, Yong-Suk

    2006-12-01

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. Among the virulence factors, ApxIIA, a bacterial exotoxin, is reportedly expressed in many serotypes and is considered as a candidate for the development of a vaccine against the bacterial infection. Previously, we isolated a field strain of A. pleuropneumoniae serotype 2 in Korea and characterized its exotoxins to develop an oral vaccine. In this study, we initially confirmed the immunogenicity of ApxIIA expressed in Escherichia coli. We then developed transgenic tobacco expressing ApxIIA and tested its efficacy to induce a protective immune response against A. pleuropneumoniae infection after oral administration of the plant powder. We observed that protective immune responses were induced in mice after oral administration of the plant powder once a week for 4 weeks. Immunoassays revealed that the levels of antigen-specific immunoglobulin G against ApxIIA increased in mice that were fed a powder made from the transgenic plant, but not in mice fed a powder made from wild-type tobacco. Additionally, mice fed the transgenic plant powder were protected from an injection of a lethal dose of A. pleuropneumoniae. These results support that the transgenic plant may be a suitable candidate for an oral vaccine that could be used effectively against A. pleuropneumoniae infection.

  3. Randomised controlled trial to compare safety and efficacy of vaginal versus oral route of misoprostol for induction of labour in term pregnancy with unfavourable cervix

    Directory of Open Access Journals (Sweden)

    Parminder Kaur

    2015-12-01

    Conclusions: Oral misoprostol has a better safety profile than vaginal route as the incidence of hyperstimulation and tachysystole was significantly more in vaginal group, although there were no significant differences in the maternal and neonatal outcomes. [Int J Reprod Contracept Obstet Gynecol 2015; 4(6.000: 1988-1992

  4. Induction of toxin-specific neutralizing immunity by molecularly uniform rice-based oral cholera toxin B subunit vaccine without plant-associated sugar modification.

    Science.gov (United States)

    Yuki, Yoshikazu; Mejima, Mio; Kurokawa, Shiho; Hiroiwa, Tomoko; Takahashi, Yuko; Tokuhara, Daisuke; Nochi, Tomonori; Katakai, Yuko; Kuroda, Masaharu; Takeyama, Natsumi; Kashima, Koji; Abe, Michiyo; Chen, Yingju; Nakanishi, Ushio; Masumura, Takehiro; Takeuchi, Yoji; Kozuka-Hata, Hiroko; Shibata, Hiroaki; Oyama, Masaaki; Tanaka, Kunisuke; Kiyono, Hiroshi

    2013-09-01

    Plants have been used as expression systems for a number of vaccines. However, the expression of vaccines in plants sometimes results in unexpected modification of the vaccines by N-terminal blocking and sugar-chain attachment. Although MucoRice-CTB was thought to be the first cold-chain-free and unpurified oral vaccine, the molecular heterogeneity of MucoRice-CTB, together with plant-based sugar modifications of the CTB protein, has made it difficult to assess immunological activity of vaccine and yield from rice seed. Using a T-DNA vector driven by a prolamin promoter and a signal peptide added to an overexpression vaccine cassette, we established MucoRice-CTB/Q as a new generation oral cholera vaccine for humans use. We confirmed that MucoRice-CTB/Q produces a single CTB monomer with an Asn to Gln substitution at the 4th glycosylation position. The complete amino acid sequence of MucoRice-CTB/Q was determined by MS/MS analysis and the exact amount of expressed CTB was determined by SDS-PAGE densitometric analysis to be an average of 2.35 mg of CTB/g of seed. To compare the immunogenicity of MucoRice-CTB/Q, which has no plant-based glycosylation modifications, with that of the original MucoRice-CTB/N, which is modified with a plant N-glycan, we orally immunized mice and macaques with the two preparations. Similar levels of CTB-specific systemic IgG and mucosal IgA antibodies with toxin-neutralizing activity were induced in mice and macaques orally immunized with MucoRice-CTB/Q or MucoRice-CTB/N. These results show that the molecular uniformed MucoRice-CTB/Q vaccine without plant N-glycan has potential as a safe and efficacious oral vaccine candidate for human use.

  5. Efficiency of systemic versus intralesional bone marrow-derived stem cells in regeneration of oral mucosa after induction of formocresol induced ulcers in dogs

    Directory of Open Access Journals (Sweden)

    Lobna A Aly

    2014-01-01

    Full Text Available Background: Bone marrow mesenchymal stem cells (BMSCs are the key to regenerative wound healing. MSCs have spatial memory and respond to local environment. The goal of this study was to evaluate the use of systemic and intralesional transplantation of BMSCs for regeneration of oral mucosa in an in vivo dog model. Materials and Methods: Transplantation of undifferentiated green fluorescent protein (GFP-labeled autologous BMSCs systemically, submucosally or vehicle (saline was injected around the chemically induced oral ulcer in each group of 18 adult dogs. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF and collagen genes was detected in biopsies from all ulcers. One way ANOVA was used to compare between means of the three groups. Results were considered significant at P < 0.05. Results: Flow cytometric analysis of the MSCs at the passage 3 showed that these cells were negative for CD45 (2.39%. They expressed high levels of CD29 (98.34%. Frozen fluorescence microscopy of sections of the cell-treated oral tissue of all groups indicated that the GFP-transduced implanted cells were integrated within the transplanted tissues. The treatment resulted in dramatic wound edge activation and resurfacing of oral mucosa wound. Conclusion: Our results revealed that BMSCs may be labeled with (GFP, in order to know the distribution of these cells after administration, and suggest that intralesional administration is an appropriate procedure to achieve acceptable regeneration of the previously injured oral mucosa more than systemic route.

  6. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota

    DEFF Research Database (Denmark)

    Elison, Emma; Vigsnæs, Louise K.; Rindom Krogsgaard, Laura

    2016-01-01

    in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show...

  7. Immunomodulation of Experimental Autoimmune Encephalomyelitis by Oral Administration of Copolymer 1

    Science.gov (United States)

    Teitelbaum, Dvora; Arnon, Ruth; Sela, Michael

    1999-03-01

    The activity of copolymer 1 (Cop 1, Copax-one, glatiramer acetate) in suppressing experimental autoimmune encephalomyelitis (EAE) and in the treatment of multiple sclerosis patients when injected parenterally has been extensively demonstrated. In the present study we addressed the question of whether Cop 1 can induce oral tolerance to EAE similar to myelin basic protein (MBP). We now have demonstrated that oral Cop 1 inhibited EAE induction in both rats and mice. Furthermore, oral Cop 1 was more effective than oral MBP in suppressing EAE in rats. The beneficial effect of oral Cop 1 was found to be associated with specific inhibition of the proliferative and Th1 cytokine secretion responses to MBP of spleen cells from Cop 1-fed mice and rats. In all of these assays, oral Cop 1 was more effective than oral MBP. The tolerance induced by Cop 1 could be adoptively transferred with spleen cells from Cop 1-fed animals. Furthermore, Cop 1-specific T cell lines, which inhibit EAE induction in vivo, could be isolated from the above spleen cells. These T cell lines secrete the anti-inflammatory cytokines IL-10 and transforming growth factor type β , but not IL-4, in response to both Cop 1 and MBP. In conclusion, oral Cop 1 has a beneficial effect on the development of EAE that is associated with down-regulation of T cell immune responses to MBP and is mediated by Th2/3 type regulatory cells. These results suggest that oral administration of Cop 1 may modulate multiple sclerosis as well.

  8. Induction of immune responses in mice and pigs by oral administration of classical swine fever virus E2 protein expressed in rice calli.

    Science.gov (United States)

    Jung, Myunghwan; Shin, Yun Ji; Kim, Ju; Cha, Seung-Bin; Lee, Won-Jung; Shin, Min-Kyoung; Shin, Seung Won; Yang, Moon-Sik; Jang, Yong-Suk; Kwon, Tae-Ho; Yoo, Han Sang

    2014-12-01

    Classical swine fever (CSF), caused by the CSF virus (CSFV), is a highly contagious disease in pigs. In Korea, vaccination using a live-attenuated strain (LOM strain) has been used to control the disease. However, parenteral vaccination using a live-attenuated strain still faces a number of problems related to storage, cost, injection stress, and differentiation of CSFV infected and vaccinated pigs. Therefore, two kinds of new candidates for oral vaccination have been developed based on the translation of the E2 gene of the SW03 strain, which was isolated from an outbreak of CSF in 2002 in Korea, in transgenic rice calli (TRCs) from Oriza sativa L. cv. Dongjin to express a recombinant E2 protein (rE2-TRCs). The expression of the recombinant E2 protein (rE2) in rE2-TRCs was confirmed using Northern blot, SDS-PAGE, and Western blot analysis. Immune responses to the rE2-TRC in mice and pigs were investigated after oral administration. The administration of rE2-TRCs increased E2-specific antibodies titers and antibody-secreting cells when compared to animals receiving the vector alone (p Pigs receiving rE2-TRCs also showed an increase in IL-8, CCL2, and the CD8+ subpopulation in response to stimulation with prE2. These results suggest that oral administration of rE2-TRCs can induce E2-specific immune responses.

  9. Efeitos da suplementação oral de L-carnitina associada ao treinamento físico na tolerância ao exercício de pacientes com doença pulmonar obstrutiva crônica Influence of oral L-carnitine supplementation combined with physical training on exercise tolerance in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Audrey Borghi Silva

    2003-12-01

    526 ± 64.3 respectively. In addition, heart rates during physical training sessions were found to be significantly lower in G1 when compared to G2. There were no significant changes in spirometric variables, oxygen saturation or dyspnea in any group. Plasma levels of free L-carnitine were found to increase only in G3 (59.2 ± 13.8 to 102.3 ± 15.3 mmol/L. CONCLUSION: Oral L-carnitine supplementation combined with physical training may improve tolerance to physical exertion in chronic obstructive pulmonary disease patients.

  10. ER-Dependent Ca++-mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells.

    Science.gov (United States)

    Lu, Yao-Cheng; Lin, Meng-Liang; Su, Hong-Lin; Chen, Shih-Shun

    2016-02-01

    Release of calcium (Ca(++)) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca(++) release dantrolene and inhibitor of mitochondrial Ca(++) uptake Ru-360, we demonstrated that Ca(++) release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose-regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca(++) increase and apoptosis, but did not attenuate the increase in cytosolic Ca(++) level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM)-mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by treatment with N-acetylcysteine, a ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. Taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca(++)-mediated ROS production.

  11. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Herman, Gary A; Bergman, Arthur; Stevens, Catherine;

    2006-01-01

    CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce...

  12. Influência da amamentação nos resultados do teste oral de tolerância à glicose pós-parto de mulheres com diabetes mellitusgestacional

    OpenAIRE

    Dijigow,Fernanda Borges; Paganoti,Cristiane de Freitas; Costa,Rafaela Alkmin da; Francisco,Rossana Pulcineli Vieira; Zugaib, Marcelo

    2015-01-01

    Resumo OBJETIVO: Avaliar a influência da amamentação nos resultados do teste oral de tolerância à glicose pós-parto (TTGp) de mulheres que apresentaram diabetes gestacional atendidas em unidade terciária do município de São Paulo. MÉTODOS: Foram obtidos dados de pacientes com diabetes gestacional no período de janeiro a dezembro de 2014. As informações foram obtidas por meio de acesso aos prontuários eletrônicos e pelo contato telefônico. Seguindo os critérios de inclusão adotados, 132 paci...

  13. Evaluation of intravenous hydroxylethyl starch, intravenous albumin 20%, and oral cabergoline for prevention of ovarian hyperstimulation syndrome in patients undergoing ovulation induction

    Directory of Open Access Journals (Sweden)

    Ataollah Ghahiri

    2015-01-01

    Full Text Available Background: The purpose of this study was to compare the three different strategies, intravenous (IV hydroxylethyl starch (HES, IV human albumin (HA, and oral Cabergoline (Cb in the prevention of ovarian hyperstimulation syndrome (OHSS. Materials and Methods: In this prospective randomized clinical trial, 91 women at high risk of developing OHSS were allocated into the three groups, group one received 2 vial (2 × 50 ml IV HAs, in group two, 1000 ml of 6% HES was administered IV, both groups 30 min after oocyte retrieval within 4 h. Group three, 31 infertile patients received oral Cb 0.5 mg daily for 7 days after oocyte retrieval. Patients were visited 14 ± 1 days after in-vitro fertilization and if β-human chorionic gonadotropin level >10, transvaginal ultrasonography was performed 2 weeks later to confirm intrauterine pregnancy. Patients were followed up weekly for 3 months for signs of OHSS and were also informed about the signs of OHSS and asked to contact immediately if any symptoms of were detected. Results: None of the participants in group HES developed severe OHSS and only 3 patients (10% developed mild to moderate OHSS. The incident of severe OHSS was significantly higher in albumin group compared to Cb and HES group (P = 0.033 and P < 0.001, respectively. Also, the probability of developing severe OHSS was higher in Cb group than group HES (P = 0.031. Conclusion: The findings from this study suggest that administration of 1000 ml of HES 6% has a higher prophylactic effect compared to administration of IV HA and oral Cb.

  14. A prospective longitudinal study of the clinical outcomes from cryptococcal meningitis following treatment induction with 800 mg oral fluconazole in Blantyre, Malawi.

    Directory of Open Access Journals (Sweden)

    Camilla Rothe

    Full Text Available Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data.From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation.Sixty patients were recruited. 26/60 (43% died by 4 weeks. 35/60 (58.0% and 43/56 (77% died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score 3 of 5 and confusion (Abbreviated Mental Test Score <8 of 10 were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes.Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit.

  15. Comparative evaluation of 50 microgram oral misoprostol and 25 microgram intravaginal misoprostol for induction of labour at term: a randomized trial.

    Science.gov (United States)

    Rahman, Hafizur; Pradhan, Anup; Kharka, Latha; Renjhen, Prachi; Kar, Sumit; Dutta, Sudip

    2013-05-01

    Objectifs : Évaluer et comparer l’efficacité et l’innocuité de 50 µg de misoprostol par voie orale et de 25 µg de misoprostol par voie intravaginale pour le déclenchement du travail à terme. Méthodes : Cet essai clinique randomisé n’ayant pas été mené à l’insu portait sur 228 femmes enceintes à terme qui présentaient des indications obstétricales ou médicales en ce qui concerne le déclenchement du travail. Ces femmes ont été affectées au hasard à un groupe devant prendre 50 µg de misoprostol par voie orale (deux comprimés de 25 µg) ou à un groupe devant se faire insérer un comprimé de 25 µg de misoprostol dans le cul-de-sac postérieur du vagin. Dans chacun de ces groupes, l’administration de la même dose de misoprostol a été répétée toutes les quatre heures jusqu’à ce que des contractions utérines régulières aient été établies ou jusqu’à l’administration d’un maximum de cinq doses. Le délai jusqu’à l’accouchement et les données quant aux issues ont été comparés chez ces groupes. Résultats : Huit (3,5 %) de ces 228 femmes ont été exclues de l’analyse puisqu’elles ont révoqué leur consentement à la suite de la randomisation. L’intervalle déclenchement-accouchement moyen était semblable dans les deux groupes (21,22 heures au sein du groupe « oral » vs 20,15 heures au sein du groupe « vaginal »; P = 0,58). Aucune différence significative n’a été constatée entre les deux groupes en ce qui concerne le nombre de femmes ayant accouché dans les 24 heures ou ayant nécessité une accélération du travail à l’oxytocine, le mode d’accouchement et les issues néonatales (P > 0,05). Une hyperstimulation utérine s’est manifestée chez deux des femmes qui avaient reçu du misoprostol par voie vaginale; toutefois, aucune des femmes ayant reçu du misoprostol par voie orale n’a été affectée par un tel phénomène. Conclusion : Le misoprostol administr

  16. A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, with respect to efficacy, cycle control, and tolerance.

    Science.gov (United States)

    Endrikat, J; Müller, U; Düsterberg, B

    1997-03-01

    The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other

  17. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization.

    Science.gov (United States)

    Tournaye, Herman; Sukhikh, Gennady T; Kahler, Elke; Griesinger, Georg

    2017-05-01

    Is oral dydrogesterone 30 mg daily (10 mg three times daily [TID]) non-inferior to micronized vaginal progesterone (MVP) 600 mg daily (200 mg TID) for luteal support in in vitro fertilization (IVF), assessed by the presence of fetal heartbeats determined by transvaginal ultrasound at 12 weeks of gestation? Non-inferiority of oral dydrogesterone versus MVP was demonstrated at 12 weeks of gestation, with a difference in pregnancy rate and an associated confidence interval (CI) that were both within the non-inferiority margin. MVP is routinely used in most clinics for luteal support in IVF, but it is associated with side effects, such as vaginal irritation and discharge, as well as poor patient acceptance. Dydrogesterone may be an alternative treatment due to its patient-friendly oral administration. Lotus I was an international Phase III randomized controlled trial, performed across 38 sites, from August 2013 to March 2016. Subjects were premenopausal women (>18 to Pharmaceuticals Division. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Besins, Ferring and Mithra (now Allergan) and H.T. has received consultancy fees from Finox, Ferring, Abbott, ObsEva and Ovascience. G.S. has nothing to disclose. E.K. is an employee of Abbott GmbH. G.G. has received investigator fees from Abbott during the conduct of the study; outside of this submitted work, G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, Glycotope, as well as personal fees from VitroLife, NMC Healthcare LLC, ReprodWissen LLC and ZIVA LLC. NCT01850030 (clinicaltrials.gov). 19 April 2013. 23 August 2013.

  18. Hypersensitivity Reaction and Tolerance Induction to Ethambutol

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    Josefina Rodrigues Cernadas

    2013-01-01

    Full Text Available Tuberculosis remains the leading cause of death worldwide from any infectious agent and the alarming increase in the annual incidence of new cases has been described as a global emergency. Mycobacterium infection requires simultaneous administration of multiple drugs. Although the majority of treatment courses progress with minor side effects, adverse reactions to antituberculosis drugs occur in about 5% of treated patients and can be responsible for cessation or switching the therapy. Both nonimmediate (mostly maculopapular rash and immediate reactions (urticarial reactions have been described with these drugs. The main problem is the occurrence of reactions while the patient is on treatment with multiple drugs. The diagnosis of the culprit drug is mostly based on stopping all medication, followed by the reintroduction of each drug with a time interval of four to five days. An alternative drug should be the first approach if it is equally effective. Most of the times, none of the alternative drugs are as effective as the culprit. If this is the case, a desensitization procedure should be performed. The authors describe a case of a woman with Mycobacterium avium complex (MAC infection, to whom treatment with ethambutol was crucial to recovery, and present a modified desensitization protocol to this drug.

  19. Safety and Tolerability of Essential Oil from Cinnamomum zeylanicum Blume Leaves with Action on Oral Candidosis and Its Effect on the Physical Properties of the Acrylic Resin

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    Julyana de Araújo Oliveira

    2014-01-01

    Full Text Available The anti-Candida activity of essential oil from Cinnamomum zeylanicum Blume, as well as its effect on the roughness and hardness of the acrylic resin used in dental prostheses, was assessed. The safety and tolerability of the test product were assessed through a phase I clinical trial involving users of removable dentures. Minimum inhibitory concentration (MIC and minimum fungicidal concentrations (MFC were determined against twelve Candida strains. Acrylic resin specimens were exposed to artificial saliva (GI, C. zeylanicum (GII, and nystatin (GIII for 15 days. Data were submitted to ANOVA and Tukey posttest (α=5%. For the phase I clinical trial, 15 healthy patients used solution of C. zeylanicum at MIC (15 days, 3 times a day and were submitted to clinical and mycological examinations. C. zeylanicum showed anti-Candida activity, with MIC = 625.0 µg/mL being equivalent to MFC. Nystatin caused greater increase in roughness and decreased the hardness of the material (P<0.0001, with no significant differences between GI and GII. As regards the clinical trial, no adverse clinical signs were observed after intervention. The substance tested had a satisfactory level of safety and tolerability, supporting new advances involving the clinical use of essential oil from C. zeylanicum.

  20. Gravitational induction

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    Bini, Donato; Chicone, Carmen; Mashhoon, Bahram

    2008-01-01

    We study the linear post-Newtonian approximation to general relativity known as gravitoelectromagnetism (GEM); in particular, we examine the similarities and differences between GEM and electrodynamics. Notwithstanding some significant differences between them, we find that a special nonstationary metric in GEM can be employed to show {\\it explicitly} that it is possible to introduce gravitational induction within GEM in close analogy with Faraday's law of induction and Lenz's law in electrodynamics. Some of the physical implications of gravitational induction are briefly discussed.

  1. Inductive reasoning.

    Science.gov (United States)

    Hayes, Brett K; Heit, Evan; Swendsen, Haruka

    2010-03-01

    Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category-based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge-based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

  2. A COMPARISON OF MIDAZOLAM AND KETAMINE PLUS MIDAZOLAM COMBINATION AS AN ORAL PREMEDICANT IN PAEDIATRIC PATIENTS

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    Krishna Prabu

    2014-08-01

    Full Text Available INTRODUCTION: Effective premedication in pediatric patients posted for elective surgeries allays patients’ anxiety and reduces risk of post-operative behavioral problems. Oral midazolam and oral ketamine are tried in different doses as pediatric premedicant, but addition of 3mg/kg of oral ketamine with 0.5 mg/kg of oral midazolam resulted in better premedication when compared to oral midazolam 0.5mg/kg or oral ketamine 6mg/kg given alone. MATERIAL AND METHODS: 60 healthy children under 1-8 yrs. age group posted for elective surgeries chosen for this study were randomly divided into two groups of 30 each. Double blinding was done using sealed envelope technique to prevent observer bias. Children with other co-existing illnesses were excluded from the study. Group KM received Ketamine 3 mg/kg and midazolam 0.5 mg/kg + atropine 20 µg/kg (oral route and Group M received midazolam 0.5 mg/kg and atropine 20 µg/kg (oral route 30 minutes before proposed induction time. Sedation score, anxiolysis score, parental separation and mask tolerance was assessed in all the patients 30 minutes after administration of the drug. RESULTS: The data collected was analyzed using SPSS statistical software. There was a statistically significant increase in sedation score at 15 and 30 minutes in group KM compared to group M. Parental separation at 30 minutes is peaceful in 30 children (100% in group KM compared to 24 children (80% in group M. CONCLUSION: The oral ketamine and midazolam combination produces significantly better anxiolysis, sedation, parental separation and mask tolerance, without hemodynamic alteration, when compared to oral midazolam (0.5mg/kg given alone.

  3. Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

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    Meng Wang

    2015-09-01

    Full Text Available L-3-n-butylphthalide (L-NBP is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40, or multiple doses of 160 mg twice daily for 7 days (n=12. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE, death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

  4. Distinct signaling pathways leading to the induction of human β-defensin 2 by stimulating an electrolyticaly-generated acid functional water and double strand RNA in oral epithelial cells.

    Science.gov (United States)

    Gojoubori, Takahiro; Nishio, Yukina; Asano, Masatake; Nishida, Tetsuya; Komiyama, Kazuo; Ito, Koichi

    2014-04-01

    Defensins, a major family of cationic antimicrobial peptides, play important roles in innate immunity. In the present study, we investigated whether double-stranded RNA (dsRNA), a by-product of RNA virus replication, can induce human β-defensins-2 (hBD-2) expression in oral epithelial cells (OECs). We also examined the hBD-2-inducible activity of acid-electrolyzed functional water (FW). The results indicated that both dsRNA- and FW-induced hBD-2 expression in OECs. The induction efficiency was much higher for FW than for dsRNA. FW-induced production of hBD-2 was clearly observed by immunofluorescence staining. A luciferase assay was performed with 1.2 kb of the 5'-untranslated region (5'-UTR) of the hBD-2 gene. The results indicated that the nuclear factor-kappa B (NF-κB)-binding site proximal to the translation initiation site was indispensable for dsRNA-stimulated hBD-2 expression, but not in the case of FW. Moreover, FW-stimulated hBD-2 expression did not depend on NF-κB activity; instead, FW inhibited NF-κB activity. Pretreatment of the cells with specific inhibitors against NF-κB further confirmed NF-κB-independent hBD-2 induction by FW. In analogy to the results for intestinal epithelial cells (IECs), the dsRNA signal, but not FW, was sensed by toll-like receptor 3 (TLR3) in OECs. These results suggested that hBD-2 expression induced by dsRNA and FW is regulated by distinct mechanisms in OECs.

  5. Intra-arterial administration of carboplatin plus lower dosage radiation of {sup 60}CO as induction treatment in advanced oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Okutomi, Tadashi; Kato, Yukihiro; Ichihara, Hideki; Kusunoki, Yukihiro; Hatakeyama, Daijiro; Yokoyama, Kyoko; Tatematsu, Norichika [Gifu Univ. (Japan). School of Medicine; Liu, Jianhua

    2000-11-01

    Conventional pre-operative chemoradiotherapy often causes severe side effects, which may result in interruption of the treatment and delay of decided operation. Carboplatin (CBDCA) is one of the effective chemotherapeutants for head and neck cancer. We treated 23 patients with advanced oral cancers by a combination of intra-arterial administration of Carboplatin and {sup 60}CO radiotherapy. The dosage of Carboplatin was between 20 mg and 35 mg per square meter of body surface. The dosage of external {sup 60}CO irradiation was 2 Gy per day and 30 to 60 Gy in total. We evaluated clinical response, toxicity and survival of this therapy of all the patients. Histologic response was also evaluated in some of them. All cancers responded to the regional chemoradiotherapy and demonstrated remission. Two (8%) completed response rate (CR) and 16 (69%) partial response rate (PR) were achieved. The accumulated five-year overall survival rate by Kaplan-Meier method was 73.9%. Fourteen patients (60.8%) showed no evidence of disease (NED) within five years after the therapy. All patients had stomatitis, but most of them were not so severe. The major hematological toxicity was leukopenia, but it was from mild to moderate and reversible. Our study showed that this therapy provided low toxicity, high clinical and histological response rate. (author)

  6. Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center

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    V M Patil

    2014-01-01

    Full Text Available Background: Recent studies indicate neoadjuvant chemotherapy (NACT can result in R0 resection in a substantial proportion of patients with technically unresectable oral cavity cancers. However, data regarding the efficacy and safety of docetaxel, cisplatin and 5 fluorouracil (TPF NACT in our setting is lacking. The present audit was proposed to evaluate the toxicities encountered during administration of this regimen. It was hypothesized that TPF NACT would be considered feasible for routine administration if an average relative dose intensity (ARDI of ≥0.90 or more in at least 70% of the patients. Materials and Methods: Technically unresectable oral cancers with Eastern Cooperative Oncology Group PS 0-2, with biopsy proven squamous cell carcinoma underwent two cycles of NACT with TPF regimen. Toxicity and response rates were noted following the CTCAE 4.03 and RECIST criteria. Descriptive analysis of completion rates (completing 2 cycles of planned chemotherapy with ARDI of 0.85 or more, reason for delay, toxicity, and response are presented. Results: The NACT was completed by all patients. The number of subjects who completed all planned cycles of chemotherapy are with the ARDI of the delivered chemotherapy been equal to or >0.85 was 11 (91.67%. All toxicity inclusive Grade 3-5 toxicity was seen in 11 patients (91.67%. The response rate of chemotherapy was 83.33%. There were three complete response, seven partial response, and two stable disease seen post NACT in this study. Conclusion: Docetaxel, cisplatin and 5 fluorouracil regimen can be routinely administered at our center with the supportive care methods and precautionary methods used in our study.

  7. Once daily oral mesalamine compared to conventional dosing for induction and maintenance of remission in ulcerative colitis: a systematic review and meta-analysis.

    Science.gov (United States)

    Feagan, Brian G; MacDonald, John K

    2012-09-01

    We systematically reviewed and compared the efficacy and safety of once daily (OD) mesalamine to conventional dosing for induction and maintenance of remission in ulcerative colitis (UC). A literature search to January 2012 identified all applicable randomized trials. Study quality was evaluated using the Cochrane risk of bias tool. The GRADE criteria were used to assess the overall quality of the evidence. Studies were subgrouped by formulation for meta-analysis. Eleven studies that evaluated 4070 patients were identified. The risk of bias was low for most factors, although five studies were single-blind and one was open-label. No difference was observed between the dosing strategies in the proportion of patients with clinical remission (relative risk [RR] 0.95; 95% confidence interval [CI] 0.82-1.10), clinical improvement (RR 0.87 95% CI 0.68-1.10), or relapse at 6 (RR 1.10; 95% CI 0.83-1.46) or 12 months (RR 0.92; 95% CI 0.83-1.03). Subgroup analyses showed no important differences in efficacy. No significant difference was demonstrated in rates of medication adherence or adverse events between OD and conventional dosing. OD mesalamine appears to be as effective and safe as conventional dosing for both the treatment of mild to moderately active UC and for maintenance of remission in quiescent UC. The failure to demonstrate a superior rate of adherence to OD dosing may be due to the high rate of adherence observed in the clinical trials environment. Future research should assess the value of OD dosing in community settings.

  8. Induction of labor with titrated oral misoprostol solution versus oxytocin in term pregnancy: randomized controlled trial Indução do trabalho de parto por meio de solução oral titulada de misoprostol versus oxitocina em gestação a termo: estudo controlado randomizado

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    Rezvan Aalami-Harandi

    2013-02-01

    Full Text Available PURPOSE: To evaluate the effectiveness and the safety of orally administered misoprostol in comparison to intravenously infused oxytocin for labor induction in term pregnant women. METHODS: Between 2008 and 2010, a total of 285 term pregnant women whom were candidate for vaginal delivery were assessed for eligibility to enter the study. Twenty five patients were excluded for different reasons; and 260 included women were randomly assigned to one of the two groups according to the method of treatment, misoprostol or oxytocin. The misoprostol group received 25 µg every 2 hours for up to 24 hours for induction. The oxytocin group received an infusion of 10 IU which was gradually increased. The time from induction to delivery and induction to the beginning of the active phase and successful inductions within 12, 18, and 24 hours were recorded. The trial is registered at irct.ir, number IRCT2012061910068N1. RESULTS: Failure of induction, leading to caesarean section was around 38.3% in the oxytocin group and significantly higher than that of the misoprostol group (20.3% (pOBJETIVO: Avaliar a eficácia e segurança do misoprostol administrado por via oral em comparação à infusão de oxitocina para a indução do trabalho de parto em gestantes a termo. MÉTODOS: Entre 2008 e 2010, um total de 285 gestantes a termo candidatas para parto vaginal foram avaliadas quanto à eligibilidade para inclusão no estudo. Vinte e cinco pacientes foram excluídas por várias razões, e as 260 mulheres incluídas foram divididas aleatoriamente em dois grupos de acordo com o método de tratamento, misoprostol ou oxitocina. O grupo tratado com o misoprostol recebeu 25 µg cada 2 horas durante um máximo de 24 horas para indução. O grupo tratado com oxitocina recebeu infusão de 10 UI, que foi aumentada gradativamente. O tempo a partir da indução até o início da fase ativa e as induções bem-sucedidas dentro de 12, 18 e 24 horas foram registrados. O ensaio foi

  9. Pharmacokinetics and Tolerability of Rufinamide Following Single and Multiple Oral Doses and Effect of Food on Pharmacokinetics in Healthy Chinese Subjects.

    Science.gov (United States)

    Xu, Mingzhen; Ni, Yang; Zhou, Ying; He, Xiaomeng; Li, Huqun; Chen, Hui; Li, Weiyong

    2016-10-01

    Rufinamide is a triazole derivative that is structurally unrelated to currently marketed antiepileptic medications for add-on treatment of seizures in the setting of Lennox-Gastaut syndrome in patients from the age of 4 years. The purpose of this study was to determine the pharmacokinetic and safety profile of single and multiple doses of rufinamide in healthy Chinese subjects. The effects of food and gender on the pharmacokinetic properties of rufinamide were also evaluated. In the single-dose study, volunteers were randomly assigned to 4 dose groups and received a single dose of 200, 400, 800, 1200 mg rufinamide tablets under fasting condition. Ten subjects in the 200-mg dose group were randomly assigned to either a high-fat or non-high-fat breakfast group in each study period. The drug administration was separated by a washout period of 7 calendar days. In the multiple-dose study, 10 subjects were administered on an empty stomach rufinamide 200 mg twice daily for 6 consecutive days. Liquid chromatography tandem mass spectrometry (LC-MS/MS) method was applied to determine plasma concentration of rufinamide. Pharmacokinetic parameters, including the maximum plasma concentration (C max), the time to peak concentration (t max), the area under the plasma concentration versus time curve from time 0 to the last measurable concentration (AUC0-t ) and from time 0 to infinity (AUC0-∞), terminal elimination half-life (t 1/2), apparent volume of distribution (V d), apparent clearance (CL), average residence time (MRT), area under the plasma concentration versus time curve from time 0 to the last measurable concentration at steady state (AUCss), peak concentration (C max,ss) and trough level concentration (C min,ss) at steady state were calculated using non-compartmental models. Tolerability was assessed based on investigator inquiries, spontaneous reports and clinical evaluations. Rufinamide displayed a dose-dependent, but sub-proportional increase in exposure

  10. A study on oral tolerance to treat traumatic brain injury in laborary%口服免疫耐受治疗颅脑创伤的实验研究

    Institute of Scientific and Technical Information of China (English)

    张洪伟; 闫华; 武俏丽; 张国斌; 刘暌; 只达石

    2011-01-01

    目的 探讨口服免疫耐受对脑损伤的治疗作用.方法 58只兔随机分为对照组、脑脊液引流组、脑脊液引流+口服组和免疫佐剂组.收集第1、3、7、14、21天血清,以ELISA法检测IL-1、IFN-γ、IL-10、TGF-β和ABAb浓度,并进行对比.结果 脯脊液引流组IL-1、IFN-γ、ABAb较对照组降低,IL-10较对照组升高;脑脊液引流+口服纰IL-1、IFN-γ、ABAb较其他组明显降低,而IL-10、TGF-β明显升高;免疫佐剂组介于对照组和脑脊液引流+口服组之间.结论 脑脊液引流对颅腩创伤有治疗作用;口服免疫耐受对颅脑创伤有治疗作用;完全弗氏佐剂部分抑制了口服免疫耐受.%Objective To explore the cerebral protective effects of oral tolerance therapy in rabbitTBI -models established by lateral fluid percussion machine.Method 58 rabbits were divided into four groups randomly( 18 in control group,15 in CSF drained group,10 in CSF drained + feed group and 15 in CSF drained + feed + immunologic adjuvant group).Rabbit's CSF were drained and injected into cistern in control group ; were drained only in CSF drained group; were drained and feed by mouth in drained + feed group;were drained and injected with 50 μg complete Freud's adjuvant under the skin of posterior foot and rabbits in drained + feed + immunologic adjuvant group.1 ml CSF was drained everyday until a week and phlebotomized and tested with ELISA to observe the changes of IL- 1,IFN -γ,lL- 10,TGF- β and ABAb at the time points of 1 d,3 d,7 d,14 d,21 d in each groups.Results Levels of IL - 1,IFN -γ and ABAb in CSF drained group were lower and levels of IL - 10 were higher than that in control group; levels of IL - 1,IFN -γ,ABAb in CSF drained + feed group were lower and levels of IL - 10,TGF - β were higher than that in any other groups significantly; levels of IL - 1,IFN - γ,ABAb in CSF drained + feed + immunologic adjuvant were lower than that in control group,while they were higher than that in

  11. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    Science.gov (United States)

    Petrò, Emiliano; Ruffini, Elena; Cappuccio, Melania; Guerini, Valeria; Belotti, Gloria; Fascendini, Sara; Licini, Cristina; Marcassa, Claudio

    2016-01-01

    Objective This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment. Methods This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer’s disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events. Results The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function. Conclusion In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in

  12. Pro-oxidant effect of α-tocopherol in patients with Type 2 Diabetes after an oral glucose tolerance test – a randomised controlled trial

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    Winterbone Mark S

    2007-02-01

    Full Text Available Abstract Background As a part of a larger study investigating the effects of α-tocopherol on gene expression in type 2 diabetics we observed a pro-oxidant effect of α-tocopherol which we believe may be useful in interpreting outcomes of large intervention trials of α-tocopherol. Methods 19 type 2 diabetes subjects were randomised into two groups taking either 1200 IU/day of α-tocopherol or a matched placebo for 4 weeks. On day 0 and 29 of this study oxidative DNA damage was assessed in mononuclear cells from fasted blood samples and following a 2 h glucose tolerance test (GTT. Results On day 0 there was no significant difference in oxidative DNA damage between the two groups or following a GTT. On day 29 there was no significant difference in oxidative DNA damage in fasted blood samples, however following a GTT there was a significant increase in oxidative DNA damage in the α-tocopherol treatment group. Conclusion High dose supplementation with α-tocopherol primes mononuclear cells from patients with type 2 diabetes for a potentially damaging response to acute hyperglycaemia.

  13. Impact of the Content of Fatty Acids of Oral Fat Tolerance Tests on Postprandial Triglyceridemia: Systematic Review and Meta-Analysis

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    Milena Monfort-Pires

    2016-09-01

    Full Text Available Whether the content of saturated (SFA, monounsaturated (MUFA, and polyunsaturated fatty acids (PUFA could differently influence postprandial triglycerides (TG is unknown. We examined possible differences in the postprandial TG response to fat tolerance tests (FTTs, in which SFA or unsaturated fatty acids were used. Crossover clinical trials investigating the effects of FTTs containing SFA and unsaturated fats on postprandial triglyceridemia in databases from 1994 until 2016 were searched. Of 356 studies, 338 were excluded and 18 were considered. TG net incremental areas under the curve were calculated using time-points or changes from baseline. Pooled effects of standardized mean differences and I2 test were used. Results: In 12 studies, responses to SFA versus PUFA meals, and in 16 studies versus MUFA meals were compared. Over 4 hours, no differences between SFA and unsaturated fats were observed. Over 8 hours a lower response to PUFA (SMD −2.28; 95%CI −4.16, −0.41 and a trend to lower response to MUFA (SMD −0.89, 95%CI −1.82, 0.04 were detected. FTTs shorter than 8 hours may not be sufficient to differentiate postprandial TG after challenges with distinct fatty acids. Clinical significance of different postprandial TG responses on cardiovascular risk in the long-term deserves investigation.

  14. Impact of the Content of Fatty Acids of Oral Fat Tolerance Tests on Postprandial Triglyceridemia: Systematic Review and Meta-Analysis

    Science.gov (United States)

    Monfort-Pires, Milena; Delgado-Lista, Javier; Gomez-Delgado, Francisco; Lopez-Miranda, José; Perez-Martinez, Pablo; Ferreira, Sandra Roberta Gouvea

    2016-01-01

    Whether the content of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) could differently influence postprandial triglycerides (TG) is unknown. We examined possible differences in the postprandial TG response to fat tolerance tests (FTTs), in which SFA or unsaturated fatty acids were used. Crossover clinical trials investigating the effects of FTTs containing SFA and unsaturated fats on postprandial triglyceridemia in databases from 1994 until 2016 were searched. Of 356 studies, 338 were excluded and 18 were considered. TG net incremental areas under the curve were calculated using time-points or changes from baseline. Pooled effects of standardized mean differences and I2 test were used. Results: In 12 studies, responses to SFA versus PUFA meals, and in 16 studies versus MUFA meals were compared. Over 4 h, no differences between SFA and unsaturated fats were observed. Over 8 h a lower response to PUFA (SMD −2.28; 95% CI −4.16, −0.41) and a trend to lower response to MUFA (SMD −0.89, 95% CI −1.82, 0.04) were detected. FTTs shorter than 8 h may not be sufficient to differentiate postprandial TG after challenges with distinct fatty acids. Clinical significance of different postprandial TG responses on cardiovascular risk in the long-term deserves investigation. PMID:27657122

  15. Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6–12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting

    Science.gov (United States)

    Childress, Ann C.; Kollins, Scott H.; Cutler, Andrew J.; Marraffino, Andrea; Sikes, Carolyn R.

    2017-01-01

    Abstract Objective: Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Methods: Children aged 6–12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). Results: The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting. Conclusions: MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 (ClinicalTrials.gov). PMID:27183299

  16. An open labeled, comparative clinical study on efficacy and tolerability of oral minipulse of steroid (OMP alone, OMP with PUVA and broad / narrow band UVB phototherapy in progressive vitiligo

    Directory of Open Access Journals (Sweden)

    Rath Namita

    2008-01-01

    Full Text Available Background: Several modalities of treatment have been tried in vitiligo with varied results; however, Indian data on comparative studies of two or more therapies are limited. Aims: We compared different phototherapy methods with an oral steroid as an adjunct to determine the method with the best tolerability and efficacy. Methods: Eighty-six patients with progressive vitiligo were randomly assigned to different study groups according to a continuous selection method over a period of one year. Group 1 was given OMP + PUVA, group 2 OMP + UVB (NB, group 3 OMP + UVB (BB and group 4 was given OMP alone. Each patient was followed up for six months and then released from treatment. Clinical evaluation was made at the end of three and six months. Results: In group 1 (OMP + PUVA, marked improvement was seen in 18.51% while moderate improvement was seen in 66.66% of the patients. Marked improvement was seen in 37.03% in group 2 (OMP + NB-UVB while 44.44% had moderate improvement. In group 3 (OMP + BB UVB, 8.33% showed marked improvement while moderate improvement was seen in 25% of the patients. Marked and moderate improvement was seen in 5 and 10% of group 4 (OMP patients, respectively. Conclusions: Our study compared four treatment modalities in vitiligo patients, out of which oral minipulse of steroids (OMP only had an adjunct value and was not very effective by itself. Narrow band UVB has a definite edge over broad band UVB and should be preferred when both options are available. NB-UVB and PUVA showed comparable efficacy.

  17. Orally-Induced Intestinal CD4+ CD25+ FoxP3+ Treg Controlled Undesired Responses towards Oral Antigens and Effectively Dampened Food Allergic Reactions.

    Directory of Open Access Journals (Sweden)

    Paola Lorena Smaldini

    Full Text Available The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response.

  18. Low-dose oral prolonged-release oxycodone/naloxone for chronic pain in elderly patients with cognitive impairment: an efficacy–tolerability pilot study

    Directory of Open Access Journals (Sweden)

    Petrò E

    2016-03-01

    (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001 were also reported. OXN-PR was well tolerated and did not worsen bowel function.Conclusion: In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in these fragile individuals.Keywords: dementia, Alzheimer’s disease, oxycodone/naloxone, elderly, cognitive impairment

  19. Inductive Learning

    Institute of Scientific and Technical Information of China (English)

    吴信东

    1993-01-01

    Machine learning(ML)is a major subfield of artificial intelligence(AI).It has been seen as a feasible way of avoiding the knowledge bottleneck problem in knowledge-based systems development.Research on ML has concentrated in the main on inductive learning,a paradigm for inducing rules from unordered sets of exmaples.AQ11 and ID3,the two most widespred algorithms in ML,are both inductive.This paper first summarizes AQ11,ID3 and the newly-developed extension matrix approach based HCV algorithm;and then reviews the recent development of inductive learing and automatic knowledge acquisition from data bases.

  20. Double-blind, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day versus a 21-day low-dose oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene.

    Science.gov (United States)

    Endrikat, J; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

    2001-08-01

    This prospective, double-blind, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day versus a 21-day oral contraceptive regimen containing 20 microg ethinyl estradiol and 75 microg gestodene. Participants took trial medication daily for 28 days, either 23 tablets with active substances plus 5 placebo tablets or 21 tablets with active substances plus 7 placebo tablets. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 4,878 treatment cycles (23-day regimen: 2,362 cycles; 21-day regimen: 2,516 cycles) were obtained from 703 participants (23-day regimen, n = 342; 21-day regimen, n = 361). Both preparations proved to be effective contraceptives and provided good cycle control. One pregnancy because of method failure was recorded in each treatment group. This resulted in a study Pearl Index of 0.5 for each treatment. For the 23-day regimen, 36.0% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 37.1% in the 21-day regimen. In the 23-day regimen group, intracyclic bleeding episodes were reported by 42.4% of the participants in Cycle 1 but only in 14% in Cycle 7 and in the 21-day regimen group by 44.6% in Cycle 1 and only 17.3% in Cycle 7. Overall, intracyclic bleeding was reported in 21.9% of the 23-day regimen cycles and in 22.7% of the 21-day regimen cycles.A greater number of 23-day regimen participants had shorter withdrawal bleeding periods than with the 21-day regimen. In significantly (p <0.0001) more cycles in the 23-day regimen group, participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day regimen group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day regimen group was 4 days and in the 21-day regimen group 5 days. Both preparations were well tolerated and showed a similar

  1. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    Science.gov (United States)

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results.

  2. Inducing rat brain CYP2D with nicotine increases the rate of codeine tolerance; predicting the rate of tolerance from acute analgesic response.

    Science.gov (United States)

    McMillan, Douglas M; Tyndale, Rachel F

    2017-08-21

    Repeated opioid administration produces analgesic tolerance, which may lead to dose escalation. Brain CYP2D metabolizes codeine to morphine, a bioactivation step required for codeine analgesia. Higher brain, but not liver, CYP2D is found in smokers and nicotine induces rat brain, but not liver, CYP2D expression and activity. Nicotine induction of rat brain CYP2D increases acute codeine conversion to morphine, and analgesia, however the role of brain CYP2D on the effects of repeated codeine exposure and tolerance is unknown. Rats were pretreated with nicotine (brain CYP2D inducer; 1mg/kg subcutaneously) or vehicle (saline; 1ml/kg subcutaneously). Codeine (40-60mg/kg oral-gavage) or morphine (20-30mg/kg oral-gavage) was administered daily and analgesia was assessed daily using the tail-flick reflex assay. Nicotine (versus saline) pretreatment increased acute codeine analgesia (1.32-fold change in AUC0-60min; p0.8), or the rate of morphine tolerance (8.1%/day versus 7.6%; p>0.9). The rate of both codeine and morphine tolerance (loss in peak analgesia from day 1 to day 4) correlated with initial analgesic response on day 1 (R=0.97, p<001). Increasing brain CYP2D altered initial analgesia and subsequent rate of tolerance. Variation in an individual's initial response to analgesic (e.g. high initial dose, smoking) may affect the rate of tolerance, and thereby the risk for dose escalation and/or opioid dependence. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Practicing induction:

    DEFF Research Database (Denmark)

    Sprogøe, Jonas; Rohde, Nicolas

    2009-01-01

    We claim that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and organization, what we call a generative dance, ignites both kinds of learning....

  4. Gravitational induction

    OpenAIRE

    Bini, Donato; Cherubini, Christian; Chicone, Carmen; Mashhoon, Bahram

    2008-01-01

    We study the linear post-Newtonian approximation to general relativity known as gravitoelectromagnetism (GEM); in particular, we examine the similarities and differences between GEM and electrodynamics. Notwithstanding some significant differences between them, we find that a special nonstationary metric in GEM can be employed to show {\\it explicitly} that it is possible to introduce gravitational induction within GEM in close analogy with Faraday's law of induction and Lenz's law in electrod...

  5. Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis

    Science.gov (United States)

    De Santis, Stefano; Borghesi, Cristina; Ricciardi, Serena; Giovannoni, Daniele; Fulvi, Alberto; Migliorino, Maria Rita; Marcassa, Claudio

    2016-01-01

    Introduction Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile. Conclusion OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function. PMID:27445495

  6. Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain: an observational analysis

    Directory of Open Access Journals (Sweden)

    De Santis S

    2016-07-01

    Full Text Available Stefano De Santis,1 Cristina Borghesi,1 Serena Ricciardi,2 Daniele Giovannoni,1 Alberto Fulvi,2 Maria Rita Migliorino,2 Claudio Marcassa3 1Palliative Care and Cancer Pain Service, Oncological Pulmonary Unit, 2Oncological Pulmonary Unit, San Camillo-Forlanini Hospitals, Rome, 3Cardiologia Fondazione Maugeri IRCCS, Novara, Italy Introduction: Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain. Methods: This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0–10 numerical rating scale and neuropathic pain (Douleur Neuropathique 4 were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form, Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed. Results: A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline; 46 (82.1% patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001, Brief Pain Inventory Short Form (P=0.0002, Symptom Distress Scale (P<0.0001, Hospital Anxiety and Depression Scale depression (P=0.0006 and anxiety (P<0.0001 subscales, and bowel function (P=0.0003. At study end, 37 (66.0% patients were satisfied/very satisfied with the new analgesic treatment

  7. Assessing oral bioaccessibility of trace elements in soils under worst-case scenarios by automated in-line dynamic extraction as a front end to inductively coupled plasma atomic emission spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Rosende, María [FI-TRACE group, Department of Chemistry, University of the Balearic Islands, Carretera de Valldemossa, km 7.5, Palma de Mallorca, Illes Balears E-07122 (Spain); Magalhães, Luis M.; Segundo, Marcela A. [REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, R. de Jorge Viterbo Ferreira, 228, Porto 4050-313 (Portugal); Miró, Manuel, E-mail: manuel.miro@uib.es [FI-TRACE group, Department of Chemistry, University of the Balearic Islands, Carretera de Valldemossa, km 7.5, Palma de Mallorca, Illes Balears E-07122 (Spain)

    2014-09-09

    Highlights: • Automatic oral bioaccessibility tests of trace metals under worst-case scenarios. • Use of intricate and realistic digestive fluids (UBM method). • Analysis of large amounts of soils (≥400 mg) in a flow-based configuration. • Smart interface to inductively coupled plasma atomic emission spectrometry. • Comparison of distinct flow systems mimicking physiological conditions. - Abstract: A novel biomimetic extraction procedure that allows for the in-line handing of ≥400 mg solid substrates is herein proposed for automatic ascertainment of trace element (TE) bioaccessibility in soils under worst-case conditions as per recommendations of ISO norms. A unified bioaccessibility/BARGE method (UBM)-like physiological-based extraction test is evaluated for the first time in a dynamic format for accurate assessment of in-vitro bioaccessibility of Cr, Cu, Ni, Pb and Zn in forest and residential-garden soils by on-line coupling of a hybrid flow set-up to inductively coupled plasma atomic emission spectrometry. Three biologically relevant operational extraction modes mimicking: (i) gastric juice extraction alone; (ii) saliva and gastric juice composite in unidirectional flow extraction format and (iii) saliva and gastric juice composite in a recirculation mode were thoroughly investigated. The extraction profiles of the three configurations using digestive fluids were proven to fit a first order reaction kinetic model for estimating the maximum TE bioaccessibility, that is, the actual worst-case scenario in human risk assessment protocols. A full factorial design, in which the sample amount (400–800 mg), the extractant flow rate (0.5–1.5 mL min{sup −1}) and the extraction temperature (27–37 °C) were selected as variables for the multivariate optimization studies in order to obtain the maximum TE extractability. Two soils of varied physicochemical properties were analysed and no significant differences were found at the 0.05 significance level

  8. [Oral rehydration immediately after appendectomy].

    Science.gov (United States)

    Azabache, W; Johanson, L

    1989-01-01

    An experimental study of 20 patients with appendicitis was carried out in order to know if after the appendectomy they tolerate the hidratation with rehidratant salts by mouth in place of endovenous hydratation. The oral hydratation was indicated in all the cases immediately after the operation and only was one failure (5%). In the 95% the oral hydratation was tolerated, 45% without gastric symptoms, 35% with mild gastric symptoms and in 15% with moderate gastric symptoms. The association of gentamycin-metronidazol administered by intramuscular and oral way respectively was used in 100% of the patients. In 80% as profilaxis and in 20% as treatment. Two cases had complication as sepsis of the wound one of the profilactic group (5.9%) and another of the treatment group. In conclusion the oral hydratation with rehydrating salts were tolerated for the patients immediately after the appendectomy.

  9. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    . The method has proven to give successful results in brazing tube-plate joints of copper-brass, copper-stainless steel, stainless steel-brass, and stainless steel-stainless steel. A new design of an adjustable flux concentrator for induction heating tube-to-plate joints is proposed and tested on a variety......Induction brazing is a fast and appropriate method for industrial joining of complex geometries and metal combinations. In all types of brazing processes it is important to heat the joint interface of the two materials to the same, high temperature. If one of the specimens is warmer than the other...... materials has large influence on the heating time and temperature distribution in induction heating. In order to ensure high and uniform temperature distribution near the interface of a joint between dissimilar materials the precise coil geometry and position is of great importance. The present report...

  10. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2013-01-01

    Full Text Available Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM. The use of continuous blood glucose monitoring (CGM, among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS and calculate homeostatic model assessment (HOMA, and the quantitative insulin sensitivity check index (QUICKI was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years were investigated. Using OGTT, (25% had impaired fasting blood (plasma glucose concentration (BG (>5.6 mmol/L. 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic and two had impaired glucose tolerance (IGT (BG > 7.8 and 11.1 mmol/L and 9 with IGT (56%. HOMA and QUICKI revealed levels 0.33 (0.36 ± 0.03, respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B% on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01 and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001. Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01 as well as with the average BG recorded by CGM (r = 0.75, P < 0.01. Conclusion: CGM has proven to

  11. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  12. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  13. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  14. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  15. Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting.

    Science.gov (United States)

    Childress, Ann C; Kollins, Scott H; Cutler, Andrew J; Marraffino, Andrea; Sikes, Carolyn R

    2017-02-01

    Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ).

  16. Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome: a SYSDIET sub-study.

    Science.gov (United States)

    Leder, Lena; Kolehmainen, Marjukka; Narverud, Ingunn; Dahlman, Ingrid; Myhrstad, Mari C W; de Mello, Vanessa D; Paananen, Jussi; Carlberg, Carsten; Schwab, Ursula; Herzig, Karl-Heinz; Cloetens, Lieselotte; Storm, Matilda Ulmius; Hukkanen, Janne; Savolainen, Markku J; Rosqvist, Fredrik; Hermansen, Kjeld; Dragsted, Lars O; Gunnarsdottir, Ingibjörg; Thorsdottir, Inga; Risérus, Ulf; Åkesson, Björn; Thoresen, Magne; Arner, Peter; Poutanen, Kaisa S; Uusitupa, Matti; Holven, Kirsten B; Ulven, Stine M

    2016-01-01

    Diet has a great impact on the risk of developing features of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVD). We evaluated whether a long-term healthy Nordic diet (ND) can modify the expression of inflammation and lipid metabolism-related genes in peripheral blood mononuclear cells (PBMCs) during a 2-h oral glucose tolerance test (OGTT) in individuals with MetS. A Nordic multicenter randomized dietary study included subjects (n = 213) with MetS, randomized to a ND group or a control diet (CD) group applying an isocaloric study protocol. In this sub-study, we included subjects (n = 89) from three Nordic centers: Kuopio (n = 26), Lund (n = 30), and Oulu (n = 33) with a maximum weight change of ±4 kg, high-sensitivity C-reactive protein concentration ≤10 mg L(-1), and baseline body mass index expression analysis was measured by quantitative real-time polymerase chain reaction (qPCR). We analyzed the mRNA expression changes of 44 genes before and after a 2hOGTT at the beginning and the end of the intervention. The healthy ND significantly down-regulated the expression of toll-like receptor 4 (TLR4), interleukin 18 (IL18), and thrombospondin receptor (CD36) mRNA transcripts and significantly up-regulated the expression of peroxisome proliferator-activated receptor delta (PPARD) mRNA transcript after the 2hOGTT compared to the CD. A healthy ND is able to modify the gene expression in PBMCs after a 2hOGTT. However, more studies are needed to clarify the biological and clinical relevance of these findings.

  17. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.

    Science.gov (United States)

    Pisprasert, Veeradej; Ingram, Katherine H; Lopez-Davila, Maria F; Munoz, A Julian; Garvey, W Timothy

    2013-04-01

    OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.

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

    Science.gov (United States)

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

    2014-10-15

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

  19. Dual Inverter-Fed Topology Analysis and Fault-Tolerant Algorithm Research for an Open-End Winding Induction Motor%开绕组电机双逆变器拓扑分析与容错算法研究

    Institute of Scientific and Technical Information of China (English)

    周剑敏

    2014-01-01

    The dual inverter-fed topology based on the open-end winding induction motor could effectively increase the output voltage and the output level. An electrical flow simulation model of the open-end winding induction motor was built by using the linear transformer and the controlled current source in the MATLAB/Simulink. The mathemati-cal model of the dual inverter-fed topology was analyzed. In view of the fault-tolerant performance,a SVPWM fault-tolerant control algorithm based on the reference voltage vector decoupling was proposed,and an experimental platform was constructed. The simulation results and experimental results verified the effectiveness of this simulation model and the fault-tolerant control algorithm.%基于开绕组电机的双逆变器拓扑能够有效提高输出电压等级与输出电平数,利用MATLAB环境下的线性变压器、受控电流源等模块搭建了开绕组电机的电气流仿真模型。分析了双逆变器拓扑的数学模型,针对其容错特性,提出一种基于参考电压矢量解耦的SVPWM容错控制算法,并搭建实验平台进行验证。仿真结果以及实验结果验证了开绕组异步电动机仿真模型以及容错控制算法的有效性。

  20. Oral contraceptives.

    Science.gov (United States)

    Maclennan, A H

    1987-12-01

    Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen

  1. Induced tolerance from a sublethal insecticide leads to cross-tolerance to other insecticides.

    Science.gov (United States)

    Hua, Jessica; Jones, Devin K; Relyea, Rick A

    2014-04-01

    As global pesticide use increases, the ability to rapidly respond to pesticides by increasing tolerance has important implications for the persistence of nontarget organisms. A recent study of larval amphibians discovered that increased tolerance can be induced by an early exposure to low concentrations of a pesticide. Since natural systems are often exposed to a variety of pesticides that vary in mode of action, we need to know whether the induction of increased tolerance to one pesticide confers increased tolerance to other pesticides. Using larval wood frogs (Lithobates sylvaticus), we investigated whether induction of increased tolerance to the insecticide carbaryl (AChE-inhibitor) can induce increased tolerance to other insecticides that have the same mode of action (chlorpyrifos, malathion) or a different mode of action (Na(+)channel-interfering insecticides; permethrin, cypermethrin). We found that embryonic exposure to sublethal concentrations of carbaryl induced higher tolerance to carbaryl and increased cross-tolerance to malathion and cypermethrin but not to chlorpyrifos or permethrin. In one case, the embryonic exposure to carbaryl induced tolerance in a nonlinear pattern (hormesis). These results demonstrate that that the newly discovered phenomenon of induced tolerance also provides induced cross-tolerance that is not restricted to pesticides with the same mode of action.

  2. Induction practice -

    DEFF Research Database (Denmark)

    Rohde, Nicolas; Sprogøe, Jonas

    2007-01-01

    that induction potentially triggers both individual and organizational learning and by drawing on practice-based theory we discuss how the interplay between individual and the organization, what we call agenerative dance, ignites both kinds of learning. We focus on and describe the interplay , ignites both kinds...... of learning. We focus on and describe the interplay that takes place in particular induction events and analyze the "dance" through the lens of learning. The paper concludes with a brief discussion about the implications for practitioners and the challenges and future research prospects we have encountered....... We draw on an empirical enquiry in two organizational settings, a Danish management consulting company and a German retail bank....

  3. Evaluación crítica del test de tolerancia oral a la glucosa para el diagnóstico de resistencia insulínica en pacientes con síndrome de ovario poliquístico Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Cecilia E. Calvar

    2007-02-01

    Full Text Available El test de tolerancia oral a la glucosa (TTOG es el más frecuentemente utilizado en la práctica clínica para el diagnóstico de resistencia insulínica (RI. El objetivo del presente trabajo fue la evaluación de la utilidad de los índices basales e índices TTOG, en mujeres con síndrome de ovario poliquístico (SOP y del valor predictivo de los índices basales sobre la glucemia a los 120 minutos postprandial (G 120. Se estudiaron 114 pacientes con diagnóstico de SOP y 29 mujeres normales. A todas se les realizó un TTOG. Se dosó insulina y glucosa séricas cada 30 min durante las 2 horas del test y se determinaron los siguientes índices: Indices basales: GLU/lNS (glucemia en ayunas / insulinemia en ayunas, HOMA (modelo homeostático y QUICKI (índice cuantitativo de sensibilidad insulínica e índices TTOG: AI (área bajo la curva de insulina e ISI composite (índice de sensibilidad insulínica. Se observaron correlaciones significativas entre los índices basales y los índices TTOG. Hubo 9 pruebas con índices basales normales que presentaban índice TTOG patológicos. Ninguna paciente con niveles de insulina menores a 9.9 Ul/ml presentó RI, mientras que todas las pacientes con niveles de insulina mayores a 18.4 Ul/ml tuvieron RI. Catorce pacientes (10.5% presentaron G 120 ³ a 140 mg%. En 4 de los 14 casos (12.2%, los valores basales no hicieron sospechar la posibilidad del diagnóstico de hiperglucemia post prandial. En conclusión, en pacientes con SOP, los índices basales son útiles para diagnosticar RI. Proponemos realizar TTOG para diagnóstico de RI en aquellas pacientes que presenten insulinemias en ayunas entre 9.9 y 18.4 Ul/ml. En pacientes con SOP, se recomienda la evaluación periódica de la G 120.Oral glucose tolerance test (OGTT is the most commonly used method to evaluate insulin resistance (IR in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in

  4. Oral Medication

    Science.gov (United States)

    ... Size: A A A Listen En Español Oral Medication The first treatment for type 2 diabetes blood ... new — even over-the-counter items. Explore: Oral Medication How Much Do Oral Medications Cost? Save money ...

  5. Oral myiasis

    OpenAIRE

    Thalaimalai Saravanan; Mathan A Mohan; Meera Thinakaran; Saneem Ahammed

    2015-01-01

    Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability ...

  6. Towards Tolerance

    NARCIS (Netherlands)

    Lisette Kuyper; Jurjen Iedema; Saskia Keuzenkamp

    2013-01-01

    Across Europe, public attitudes towards lesbian, gay and bisexual (LGB) individuals range from broad tolerance to widespread rejection. Attitudes towards homosexuality are more than mere individual opinions, but form part of the social and political structures which foster or hinder the equality

  7. Repressive Tolerance

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk

    2016-01-01

    to an administrative culture of repressive tolerance of organised interests: authorities listen but only reacts in a very limited sense. This bears in it the risk of jeopardising the knowledge transfer from societal actors to administrative ditto thus harming the consultation institutions’ potential for strengthening...

  8. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    Directory of Open Access Journals (Sweden)

    Pfohl M

    2015-11-01

    Full Text Available Martin Pfohl,1 Thorsten Siegmund,2 Stefan Pscherer,3 Katrin Pegelow,4 Jochen Seufert5 1Medizinische Klinik I, Evangelisches Bethesda-Klinikum GmbH, Duisburg, Germany; 2Städtisches Klinikum München GmbH, Klinikum Bogenhausen, III. Medizinische Abteilung, München, Germany; 3Klinisches Diabeteszentrum Südostbayern, Innere Medizin – Diabetologie, Traunstein, Germany; 4Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 5Medizinische Universitätsklinik, Klinik für Innere Medizin II, Abteilung für Endokrinologie und Diabetologie, Freiburg, Germany Background: Due to the progressive nature of type 2 diabetes mellitus (T2DM, antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT or supplementary insulin therapy (SIT presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT regimen in T2DM patients in daily clinical practice. Methods: This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia, and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT. Results: A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229, and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46% to 7.73% and 7.66%, respectively (Δ mean

  9. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    Directory of Open Access Journals (Sweden)

    Saab C

    2015-02-01

    assessed. Results: Of the 4,780 patients enrolled in the Middle East, 2,513 received vildagliptin and 2,267 received other OADs. Overall, the mean (± standard deviation age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, P<0.0001 and secondary (54.8% versus 29.9%, P<0.0001 endpoints was higher with vildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75–2.25 and 2.8 (95% confidence interval 2.5–3.2, respectively, in favor of vildagliptin. Vildagliptin achieved a numerically greater reduction in HbA1c (1.7% from baseline versus comparator OADs (1.4%. The overall incidence of adverse events was comparable between studied cohorts. Conclusion: In real life, treatment with vildagliptin was associated with a higher proportion of patients with T2DM achieving better glycemic control without tolerability issues in the Middle East. Keywords: dipeptidyl peptidase-4, Middle East, oral antidiabetic drugs, real world, type 2 diabetes mellitus, vildagliptin

  10. An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder

    Institute of Scientific and Technical Information of China (English)

    Yi Zheng; Jian-Min Liang; Hong-Yun Gao; Zhi-Wei Yang; Fu-Jun Jia; Yue-Zhu Liang; Fang Fang

    2015-01-01

    Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children.This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.Methods: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children.Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg).The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline.Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations,and safety at week 12 compared with baseline.Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.Results: A total of 128 patients were evaluated with cognitive assessments.The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4;P < 0.0001).Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline.A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline.Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline.No serious adverse events and deaths were reported during the study.Conclusions: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese

  11. An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder.

    Science.gov (United States)

    Zheng, Yi; Liang, Jian-Min; Gao, Hong-Yun; Yang, Zhi-Wei; Jia, Fu-Jun; Liang, Yue-Zhu; Fang, Fang; Li, Rong; Xie, Sheng-Nan; Zhuo, Jian-Min

    2015-11-20

    Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The

  12. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    Science.gov (United States)

    Saab, Charles; Al-Saber, Feryal A; Haddad, Jihad; Jallo, Mahir Khalil; Steitieh, Habib; Bader, Giovanni; Ibrahim, Mohamed

    2015-01-01

    Background Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs) versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates). Methods Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies) based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain ≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1c <7% without hypoglycemia or weight gain. Change in HbA1c from baseline to study endpoint and safety were also assessed. Results Of the 4,780 patients enrolled in the Middle East, 2,513 received vildagliptin and 2,267 received other OADs. Overall, the mean (± standard deviation) age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, P<0.0001) and secondary (54.8% versus 29.9%, P<0.0001) endpoints was higher with vildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75–2.25) and 2.8 (95% confidence interval 2.5–3

  13. Induction Brazing

    DEFF Research Database (Denmark)

    Henningsen, Poul

    , or if the hottest area is located outside the joint interface, a number of defects may appear: the braze metal may flow away from the joint, the flux may burn off, poor binding of the braze metal may appear or the braze metal may be overheated. Joint geometry as well as electro-magnetic properties of the work piece......Induction brazing is a fast and appropriate method for industrial joining of complex geometries and metal combinations. In all types of brazing processes it is important to heat the joint interface of the two materials to the same, high temperature. If one of the specimens is warmer than the other...

  14. Acquired thymic tolerance: role of CTLA4 in the initiation and maintenance of tolerance in a clinically relevant autoimmune disease model

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Zhang, M; Sayegh, M H;

    1999-01-01

    Injection of Ag into the thymus of adult animals induces specific systemic tolerance. The mechanisms of acquired thymic tolerance include anergy and the deletion of Ag-specific T cells. Here, we report that anergy to nominal Ag induced via acquired thymic tolerance requires CTL-associated Ag 4 (C...... for the maintenance of acquired thymic tolerance. This is the first report documenting the role of a CTLA4 negative signaling pathway in the induction of tolerance in an autoimmune disease model....

  15. Cultural conditions required for the induction of an adaptive acid-tolerance response (ATR) in Sinorhizobium meliloti and the question as to whether or not the ATR helps rhizobia improve their symbiosis with alfalfa at low pH.

    Science.gov (United States)

    Draghi, Walter O; Del Papa, María Florencia; Pistorio, Mariano; Lozano, Mauricio; de Los Angeles Giusti, María; Torres Tejerizo, Gonzalo A; Jofré, Edgardo; Boiardi, José Luis; Lagares, Antonio

    2010-01-01

    Sinorhizobium meliloti associates with Medicago and Melilotus species to develop nitrogen-fixing symbioses. The agricultural relevance of these associations, the worldwide distribution of acid soils, and the remarkable acid sensitivity of the microsymbiont have all stimulated research on the responses of the symbionts to acid environments. We show here that an adaptive acid-tolerance response (ATR) can be induced in S. meliloti, as shown previously for Sinorhizobium medicae, when the bacteria are grown in batch cultures at the slightly acid pH of 6.1. In marked contrast, no increased tolerance to hydrogen ions is obtained if rhizobia are grown in a chemostat under continuous cultivation at the same pH. The adaptive ATR appears as a complex process triggered by an increased hydrogen-ion concentration, but operative only if other--as yet unknown--concomitant factors that depend on the culture conditions are present (although not provided under continuous cultivation). Although the stability of the ATR and its influence on acid tolerance has been characterized in rhizobia, no data have been available on the effect of the adapted state on symbiosis. Coinoculation experiments showed that acid-adapted indicator rhizobia (ATR+) were present in >90% of the nodules when nodulation was performed at pH 5.6, representing a >30% increase in occupancy compared with a control test. We show that the ATR represents a clear advantage in competing for nodulation at low pH. It is not yet clear whether such an effect results from an improved performance in the acid environment during preinfection, an enhanced ability to initiate infections, or both conditions. The practical use of ATR+ rhizobia will depend on validation experiments with soil microcosms and on field testing, as well as on the possibility of preserving the physiology of ATR+ bacteria in inoculant formulations.

  16. Acid tolerance of Streptococcus macedonicus as assessed by flow cytometry and single-cell sorting.

    Science.gov (United States)

    Papadimitriou, Konstantinos; Pratsinis, Harris; Nebe-von-Caron, Gerhard; Kletsas, Dimitris; Tsakalidou, Effie

    2007-01-01

    An in situ flow cytometric viability assay employing carboxyfluorescein diacetate and propidium iodide was used to identify Streptococcus macedonicus acid tolerance phenotypes. The logarithmic-phase acid tolerance response (L-ATR) was evident when cells were (i) left to autoacidify unbuffered medium, (ii) transiently exposed to nonlethal acidic pH, or (iii) systematically grown under suboptimal acidic conditions (acid habituation). Stationary-phase ATR was also detected; this phenotype was gradually degenerated while cells resided at this phase. Single-cell analysis of S. macedonicus during induction of L-ATR revealed heterogeneity in both the ability and the rate of tolerance acquisition within clonal populations. L-ATR was found to be partially dependent on de novo protein synthesis and compositional changes of the cell envelope. Interestingly, acid-habituated cells were interlaced in lengthier chains and exhibited an irregular pattern of active peptidoglycan biosynthesis sites when probed with BODIPY FL vancomycin. L-ATR caused cells to retain their membrane potential after lethal challenge, as judged by ratiometric analysis with oxonol [DiBAC(4)(3)]. Furthermore, F-ATPase was important during the induction of L-ATR, but in the case of a fully launched response, inhibition of F-ATPase affected acid resistance only partially. Activities of both F-ATPase and the glucose-specific phosphoenolpyruvate-dependent phosphotransferase system were increased after L-ATR induction, distinguishing S. macedonicus from oral streptococci. Finally, the in situ viability assessment was compared to medium-based recovery after single-cell sorting, revealing that the culturability of subpopulations with identical fluorescence characteristics is dependent on the treatments imposed to the cells prior to acid challenge.

  17. Immune mechanisms in cerebral ischemic tolerance

    Directory of Open Access Journals (Sweden)

    Lidia eGarcia-Bonilla

    2014-03-01

    Full Text Available Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance. These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral ischemic tolerance acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish ischemic tolerance and that ischemic tolerance can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of ischemic tolerance and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies.

  18. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  19. Addressing immune tolerance issues in inflammatory bowel disease and adeno-associated virus based gene transfer

    NARCIS (Netherlands)

    Majowicz, Anna

    2014-01-01

    This thesis is focusing on cell-mediated induction of immune tolerance and consists of two parts. The studies described in Part I report the development of strategies for possible treatment of Inflammatory Bowel Diseases (IBD). Induction of immune tolerance, in IBD mouse model, with the use of regul

  20. Oral Thrush

    Science.gov (United States)

    ... feeding mothers In addition to the distinctive white mouth lesions, infants may have trouble feeding or be fussy ... candidiasis (yeast infection) patient information. American Academy of Oral & Maxillofacial Pathology. http://www.aaomp.org/public/oral-candidiasis.php. ...

  1. Extreme flooding tolerance in Rorippa.

    Science.gov (United States)

    Akman, Melis; Bhikharie, Amit; Mustroph, Angelika; Sasidharan, Rashmi

    2014-01-01

    Low oxygen stress imposed by floods creates a strong selection force shaping plant ecosystems in flood-prone areas. Plants inhabiting these environments adopt various adaptations and survival strategies to cope with increasing water depths. Two Rorippa species, R. sylvestris and R. amphibia that grow in naturally flooded areas, have high submergence tolerance achieved by the so-called quiescence and escape strategies, respectively. In order to dissect the molecular mechanisms involved in these strategies, we investigated submergence-induced changes in gene expression in flooded roots of Rorippa species. There was a higher induction of glycolysis and fermentation genes and faster carbohydrate reduction in R. amphibia, indicating a higher demand for energy potentially leading to faster mortality by starvation. Moreover, R. sylvestris showed induction of genes improving submergence tolerance, potentially enhancing survival in prolonged floods. Additionally, we compared transcript profiles of these 2 tolerant species to relatively intolerant Arabidopsis and found that only Rorippa species induced various inorganic pyrophosphate dependent genes, alternatives to ATP demanding pathways, thereby conserving energy, and potentially explaining the difference in flooding survival between Rorippa and Arabidopsis.

  2. Oral Dysfunction

    OpenAIRE

    鈴木, 規子; スズキ, ノリコ; Noriko, SUZUKI

    2004-01-01

    The major oral functions can be categorized as mastication, swallowing, speech and respiratory functions. Dysfunction of these results in dysphagia, speech disorders and abnormal respiration (such as Sleep Apnea). These functions relate to dentistry in the occurrence of : (1) oral preparatory and oral phases, (2) articulation disorders and velopharyngeal incompetence (VPI), and (3) mouth breathing, respiratory and blowing disorders. These disorders are related to oral and maxillofacial diseas...

  3. Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent

    Science.gov (United States)

    AFUWAPE, A O; TURNER, M W; STROBEL, S

    2004-01-01

    Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (β-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-β was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory

  4. 78 FR 76987 - Mandipropamid; Pesticide Tolerances

    Science.gov (United States)

    2013-12-20

    ... factors, with the exception of chemical-specific processing factors for grape wine and sherry. iii. Cancer... tolerances in or on grape at 1.4 ppm; onion, dry bulb at 0.05 ppm; onion, green at 4 ppm; okra at 1.0 ppm.... Cancer (Oral, dermal, inhalation).. Classified as not likely to be carcinogenic to humans. FQPA SF = Food...

  5. Induction of immunological tolerance to the penicilloyl antigenic determinant--IV. The effect of BPO-oligolysines and cholestanol-bearing BPO-oligolysines on murine IgE responses.

    Science.gov (United States)

    Lüscher, I F; Schneider, C H; de Weck, A L; Weber, E A

    1983-10-01

    Penta-, deca- and eicosalysine carriers were synthesized in solution and conjugated with benzylpenicillin to give BPO-conjugates of high haptenic density. Each oligolysine conjugate was prepared in two forms--with a free C-terminus and with an esterified C-terminus carrying via a benzylester bridge in essence a lipophilic cholestanol moiety [p-oxymethylbenzylcholestan-3 beta-yl succinate (OSuco group)]. Decalysines that carried a single haptenic BPO group and succinyl groups on the other amino functions were also prepared. Suppression of IgE responses was studied in BALB/c mice. It was found that BPO-specific suppression could be induced by injecting OSuco-bearing deca- or eicosalysine conjugates before immunization with BPO-Asc in A1(OH)3. The pentalysine conjugate was only slightly effective as were all OSuco-deficient conjugates. Ongoing IgE responses were only slightly suppressed and OSuco-bearing conjugates were not more effective than OSuco-deficient derivatives. When the monohaptenic OSuco-bearing decalysine, which exhibited weak tolerogenic effects on primary as well as on ongoing responses, was applied under conditions that favour suppressor T-cell induction, a pronounced unresponsiveness resulted. Direct evidence for suppressor T-cell involvement in the abrogation of anti-BPO responses by OSuco-bearing BPO-conjugates was obtained from cell transfer experiments. The study shows that relatively small haptenic conjugates, the lower limit of effectiveness being approximately represented by decalysine conjugates, may be effective tolerogens depending on the immune status.

  6. Enhanced development of dispositional tolerance to methadone by desipramine given together with methadone

    Energy Technology Data Exchange (ETDEWEB)

    Liu, S.J.; Wang, R.I.H.

    1985-02-25

    Rats given 2-day oral administration of methadone (15 mg/kg, twice on day 1 and once on day 2) by gastric tube developed dispositional tolerance to methadone analgesia as demonstrated by a decrease in analgesic response and by an increase in methadone metabolism. The increased metabolism of methadone was evidenced by a decrease in brain concentration of /sup 14/C-methadone and increases in the percentages of total /sup 14/C in liver or urine as /sup 14/C-water-soluble metabolites (/sup 14/C-WSM) after the rats were challenged with a test dose of /sup 14/C-methadone. Two-day pretreatment with a combination of desipramine (DMI) (10 mg/kg, ip) and methadone (15 mg/kg, po) enhanced the development of dispositional tolerance to methadone analgesia which was evidenced by a greater decrease in the brain concentration of methadone and a greater increase in methadone metabolism as compared to those changes in rats pretreated with only methadone. Repeated treatment with DMI alone neither decreased the analgesic effect of methadone nor stimulated methadone metabolism. It is suggested that DMI given together with methadone promoted the induction of methadone metabolism in the liver by prolonging the enzyme-stimulating state of methadone, thus enhancing the development of dispositional tolerance to methadone. 20 references, 1 figure, 1 table.

  7. Effects of chronic caffeine administration on blood glucose levels and on glucose tolerance in healthy and diabetic rats.

    Science.gov (United States)

    Urzúa, Z; Trujillo, X; Huerta, M; Trujillo-Hernández, B; Ríos-Silva, M; Onetti, C; Ortiz-Mesina, M; Sánchez-Pastor, E

    2012-01-01

    To analyse the effect of chronic caffeine use on risk reduction and prognosis of diabetes mellitus. In this 60-day study, five groups of 11 healthy male Wistar rats were selected to receive one of four doses (37.5, 56.2, 75.0 or 93.0 mg/kg per day) of caffeine orally or no caffeine (control). The effect of caffeine on glycaemia and glucose tolerance was evaluated. After 15 days, each group was treated with 60 mg/kg of streptozotocine to induce diabetes mellitus, and glycaemia and glucose tolerance were assessed for a further 45 days. In nondiabetic rats, caffeine had no effect on blood glucose. Compared with controls, the fasting blood glucose levels declined significantly in two caffeine-treated groups (93.0 mg/kg per day and 56.2 mg/kg per day) during the first 15 days following diabetes induction. Glucose tolerance was significantly improved 120 min after glucose loading in all caffeine-treated groups. The mean ± SE half-maximal effective concentration of caffeine was 35.79 ± 2.44 mg/dl. Blood glucose levels decreased, and glucose tolerance improved, in diabetic rats administered increasing doses of caffeine.

  8. Acquisition and loss of desiccation tolerance in seeds : from experimental model to biological relevance

    NARCIS (Netherlands)

    Dekkers, Bas J W|info:eu-repo/dai/nl/326091572; Costa, Maria Cecilia D; Maia, Julio; Bentsink, Leónie|info:eu-repo/dai/nl/241338735; Ligterink, Wilco; Hilhorst, Henk W M

    2015-01-01

    MAIN CONCLUSION: Besides being an important model to study desiccation tolerance, the induction of desiccation tolerance in germinated seeds may also play an ecological role in seedling establishment. Desiccation tolerance (DT) is the ability of certain organisms to survive extreme water losses with

  9. Impaired oral glucose tolerance and influencing factors in patients with impaired fasting glucose%空腹血糖受损患者糖耐量异常及影响因素分析

    Institute of Scientific and Technical Information of China (English)

    左惠芬; 刘冬青; 商晓丽; 张燕; 许丽丽; 林运

    2014-01-01

    Objective To get to know the status of impaired oral glucose tolerance (IGT) and influencing factors in patients with impaired fasting glucose (IFG). Methods IFG patients (n=337, FPG being 5.6 mmol/L-6.1 mmol/L) were chosen and their data of age, sex, diabetes family history, height, weight, waistline, blood pressure and blood fat were collected. The level of blood glucose was detected after patients taken 75 g glucose for 2 h, and the status of IGT and influencing factors were analyzed. Results Among 337 IFG patients 46.6%of them (157/337) had IGT. The proportion of overweight and obesity was 75.0%in abnormal group and 63.1%in normal group (P<0.05). The level of triglyceride (TG) was higher and level of high-density lipoprotein-cholesterol (HDL-C) was lower in abnormal group compared with normal group (P<0.05). The multi-factor Logistic regression analysis showed that age, body mass index (BMI) and TG level were influencing factors of IGT, and relative risk was, respectively, 1.06 (95%CI:1.03-1.08), 1.11 (95%CI:1.05-119) and 1.58 (95%CI:1.23-2.09). The further analysis on influencing factors in IFG patients with normal weight showed that, besides of age, TG level was a influencing factor of IGT and relative risk was 2.10 (95%CI:1.29-3.43). Conclusion There are about half of IFG patients with IGT, and BMI and TG level are influencing factors of IGT.%目的:了解空腹血糖受损(IFG)患者糖耐量异常(IGT)情况及其影响因素。方法纳入空腹血糖为5.6~6.1 mmol/L的IFG患者337例,检测患者口服75克葡萄糖后2小时血糖等资料,分析患者IGT情况及其影响因素。结果纳入的337例IFG患者中46.6%(157/337)伴有IGT。口服葡萄糖耐量异常和正常组超重和肥胖率分别为75.0%和63.1%(P<0.05);口服葡萄糖耐量异常组甘油三酯水平显著高于正常组,高密度脂蛋白胆固醇水平低于正常组,均有统计学差异(P<0.05)。多因素Logistic回归分析结

  10. Porphyromonas gingivalis-stimulated macrophage subsets exhibit differential induction and responsiveness to interleukin-10.

    Science.gov (United States)

    Foey, Andrew D; Habil, Neama; Al-Shaghdali, Khalid; Crean, StJohn

    2017-01-01

    Oral mucosal macrophages (Mϕs) determine immune responses; maintaining tolerance whilst retaining the capacity to activate defences against pathogens. Mϕ responses are determined by two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2-Mϕs. Tolerance induction is driven by M2 Mϕs, whereas M1-like Mϕs predominate in inflammation, such as that exhibited in chronic Porphyromonas gingivalis (PG) periodontal infection. Mϕ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the P. gingivalis-driven induction of and responsiveness to the suppressive, anti-inflammatory cytokine, IL-10, by Mϕ subsets. M1- and M2-like Mϕs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and Vitamin D3, respectively. Mϕ subsets were stimulated by PG-LPS in the presence or absence of IL-10. PG-LPS differentially induced IL-10 secretion and endogenous IL-10 activity in M1- and M2-like subsets. In addition, these subsets exhibited differential sensitivity to IL-10-mediated suppression of TNFα, where M2 Mϕs where sensitive to IL-10 and M1 Mϕs were refractory to suppression. In addition, this differential responsiveness to IL-10 was independent of IL-10-binding and expression of the IL-10 receptor signal transducing subunit, IL-10Rβ, but was in fact dependent on activation of STAT-3. P.gingivalis selectively tolerises regulatory M2 Mϕs with little effect on pro-inflammatory M1 Mϕs; differential suppression facilitating immunopathology at the expense of immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial

    DEFF Research Database (Denmark)

    Cannon, Christopher P; Husted, Steen; Harrington, Robert A;

    2007-01-01

    OBJECTIVES: Our goal was to compare the safety and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: AZD6140 achieves higher mean levels of p...

  12. Oral histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patil Karthikeya

    2009-01-01

    Full Text Available Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.

  13. Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

    OpenAIRE

    Alabsi, Aied M.; Kai Li Lim; Paterson, Ian C.; Rola Ali-Saeed; Bushra A. Muharram

    2016-01-01

    Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines ...

  14. Seed-based oral vaccines as allergen-specific immunotherapies.

    Science.gov (United States)

    Takaiwa, Fumio

    2011-03-01

    Plant-based vaccines have advantages over conventional vaccines in terms of scalability, lack of requirement for cold chain logistics, stability, safety, cost-effectiveness and needle-free administration. In particular, when antigen is expressed in seeds, high production is possible and immunogenicity is not lost even if stocked at ambient temperature for several years. Induction of immune tolerance (desensitization) to allergen is a principle strategy for controlling allergic diseases, and is generally carried out by subcutaneous injection. Seed-based oral administration offers a straightforward and inexpensive alternative approach to deliver vaccines effectively to the GALT without loss of activity. Consumption of transgenic seeds containing modified hypo-allergenic tolerogen or T-cell epitope peptides derived from allergens has no or very few severe side effects and can induce immune tolerance leading to reduction of allergen-specific IgE production, T-cell proliferation and release of histamine. Suppression of allergen-specific clinical symptoms results. Thus, seed-based allergy vaccines offer an innovative and convenient allergen-specific immunotherapeutic approach as an alternative to conventional allergen-specific immunotherapy.

  15. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI).

    Science.gov (United States)

    Leonardi, Sergio; Rao, Sunil V; Harrington, Robert A; Bhatt, Deepak L; Gibson, C Michael; Roe, Matthew T; Kochman, Janusz; Huber, Kurt; Zeymer, Uwe; Madan, Mina; Gretler, Daniel D; McClure, Matthew W; Paynter, Gayle E; Thompson, Vivian; Welsh, Robert C

    2010-07-01

    Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous coronary intervention (PCI). The failure of clopidogrel to provide optimal protection may be related to delayed onset of action, interpatient variability in its effect, and an insufficient level of platelet inhibition. Furthermore, the irreversible binding of clopidogrel to the P2Y(12) receptor for the life span of the platelet is associated with increased bleeding risk especially during urgent or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y(12) inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability, and preliminary efficacy of this novel antiplatelet agent in patients undergoing nonurgent PCI.

  16. Lexicographic Path Induction

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Sarnat, Jeffrey

    2009-01-01

    Programming languages theory is full of problems that reduce to proving the consistency of a logic, such as the normalization of typed lambda-calculi, the decidability of equality in type theory, equivalence testing of traces in security, etc. Although the principle of transfinite induction...... an induction principle that combines the comfort of structural induction with the expressive strength of transfinite induction. Using lexicographic path induction, we give a consistency proof of Martin-Löf’s intuitionistic theory of inductive definitions. The consistency of Heyting arithmetic follows directly...

  17. Oral administration of a cholera toxin B subunit-insulin fusion protein produced in silkworm protects against autoimmune diabetes.

    Science.gov (United States)

    Gong, Zhaohui; Jin, Yongfeng; Zhang, Yaozhou

    2005-09-22

    The oral administration of disease-specific autoantigens can induce oral immune tolerance and prevent or delay the onset of autoimmune disease symptoms. Here, we describe the construction of an edible vaccine consisting of a fusion protein composed of cholera toxin B subunit (CTB) and insulin that is produced in silkworm larvae at levels of up to 0.3 mg/ml of hemolymph. The silkworm bioreactor produced this fusion protein vaccine as the pentameric CTB-insulin form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB and insulin. Non-obese diabetic mice fed hemolymph containing microgram quantities of the CTB-insulin fusion protein showed a prominent reduction in pancreatic islet inflammation and a delay in the development of symptoms of clinical diabetes. These results demonstrate that the silkworm bioreactor is a feasible production and delivery system for an oral protein vaccine designed to develop immunological tolerance against T-cell-mediated autoimmune diabetes by regulatory T-cell induction.

  18. Inductive Monitoring System (IMS)

    Data.gov (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  19. Improving the safety of oral immunotherapy for food allergy.

    Science.gov (United States)

    Vazquez-Ortiz, Marta; Turner, Paul J

    2016-03-01

    Food allergy is a major public health problem in children, impacting upon the affected individual, their families and others charged with their care, for example educational establishments, and the food industry. In contrast to most other paediatric diseases, there is no established cure: current management is based upon dietary avoidance and the provision of rescue medication in the event of accidental reactions, which are common. This strategy has significant limitations and impacts adversely on health-related quality of life. In the last decade, research into disease-modifying treatments for food allergy has emerged, predominantly for peanut, egg and cow's milk. Most studies have used the oral route (oral immunotherapy, OIT), in which increasing amounts of allergen are given over weeks-months. OIT has proven effective to induce immune modulation and 'desensitization' - that is, an increase in the amount of food allergen that can be consumed, so long as regular (typically daily) doses are continued. However, its ability to induce permanent tolerance once ongoing exposure has stopped seems limited. Additionally, the short- and long-term safety of OIT is often poorly reported, raising concerns about its implementation in routine practice. Most patients experience allergic reactions and, although generally mild, severe reactions have occurred. Long-term adherence is unclear, which rises concerns given the low rates of long-term tolerance induction. Current research focuses on improving current limitations, especially safety. Strategies include alternative routes (sublingual, epicutaneous), modified hypoallergenic products and adjuvants (anti-IgE, pre-/probiotics). Biomarkers of safe/successful OIT are also under investigation.

  20. Lack of survival advantage in patients with advanced, resectable squamous cell carcinoma of the oral cavity receiving induction chemotherapy with cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU).

    Science.gov (United States)

    Umeda, Masahiro; Komatsubara, Hideki; Ojima, Yasutaka; Minamikawa, Tsutomu; Shigeta, Takashi; Shibuya, Yasuyuki; Yokoo, Satoshi; Komori, Takahide

    2004-01-01

    Cisplatin-based neoadjuvant chemotherapy (NAC) has been reported to increase survival of patients with nasopharyngeal carcinoma, and organ preservation in those with laryngeal carcinoma, but its efficacy for other head and neck carcinomas is still controversial. We examined the effects of NAC for patients with stage III-IV squamous cell carcinoma of the oral cavity. The patients were divided into two groups; 9 patients who underwent NAC consisting of one course of cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU) followed by surgery (NAC group), and 18 patients who underwent surgery alone (control group). Complete response (CR) was not observed, but partial response (PR) was obtained in 6 of 9 patients (33%) of the NAC group. The 3-year survival rate was 29.6% in the NAC group and 81.5% in the control group. Although any valid conclusions could not be drawn because of the small number of patients examined here, NAC with CDDP, TXT and 5FU offered no advantages over standard treatment for advanced oral cancer in terms of survival.

  1. Inductive situation calculus

    OpenAIRE

    Denecker, Marc; Ternovska, Eugenia

    2004-01-01

    Temporal reasoning has always been a major test case for knowledge representation formalisms. In this paper, we develop an inductive variant of the situation calculus in ED-logic, classical logic extended with inductive definitions. This logic has been proposed recently and is an extension of classical logic. It allows for a uniform representation of various forms of definitions, including monotone inductive definitions and non-monotone forms of inductive definitions such as iterated inductio...

  2. Hypotheses and Inductive Predictions

    NARCIS (Netherlands)

    ROMEYN, J.-W.

    2008-01-01

    ABSTRACT. This paper studies the use of hypotheses schemes in generating inductive predictions. After discussing Carnap–Hintikka inductive logic, hypotheses schemes are defined and illustrated with two partitions. One partition results in the Carnapian continuum of inductive methods, the other resul

  3. Hypotheses and Inductive Predictions

    NARCIS (Netherlands)

    ROMEYN, J.-W.

    2008-01-01

    ABSTRACT. This paper studies the use of hypotheses schemes in generating inductive predictions. After discussing Carnap–Hintikka inductive logic, hypotheses schemes are defined and illustrated with two partitions. One partition results in the Carnapian continuum of inductive methods, the other resul

  4. Inductive Reasoning and Writing

    Science.gov (United States)

    Rooks, Clay; Boyd, Robert

    2003-01-01

    Induction, properly understood, is not merely a game, nor is it a gimmick, nor is it an artificial way of explaining an element of reasoning. Proper understanding of inductive reasoning--and the various types of reasoning that the authors term inductive--enables the student to evaluate critically other people's writing and enhances the composition…

  5. Oral Immunotherapy for Treatment of Immunoglobulin E-Mediated Food Allergy: The Transition to Clinical Practice.

    Science.gov (United States)

    Pajno, Giovanni B; Cox, Linda; Caminiti, Lucia; Ramistella, Vincenzo; Crisafulli, Giuseppe

    2014-06-01

    Today, there is neither an effective nor an active treatment for food allergy. Allergy immunotherapy has been proposed as an attractive strategy to actively treat food allergy. Oral immunotherapy (OIT), also known as oral desensitization, is a method of inducing the body's immune system to tolerate a food that causes an allergic overreaction. It has been studied for the use in treatment of immunoglobulin E-mediated food allergy to the most common foods, including milk, egg, and peanut. OIT has been able to desensitize subjects to varying degrees. However, many questions remain unanswered, including efficient formulation, optimal dosing, and induction protocol to achieve full tolerance, transition of OIT to clinical practice, and maximal safety profile. This review focuses on the use of OIT as a new and active treatment for food allergy. The possibility of transition of OIT to clinical practice represents, in this field, the next pivotal step with the goal of improving the quality of life of patients with food allergy and their families.

  6. SALT TOLERANCE OF CROP PLANTS

    Directory of Open Access Journals (Sweden)

    Hamdia, M. A

    2010-09-01

    Full Text Available Several environmental factors adversely affect plant growth and development and final yield performance of a crop. Drought, salinity, nutrient imbalances (including mineral toxicities and deficiencies and extremes of temperature are among the major environmental constraints to crop productivity worldwide. Development of crop plants with stress tolerance, however, requires, among others, knowledge of the physiological mechanisms and genetic controls of the contributing traits at different plant developmental stages. In the past 2 decades, biotechnology research has provided considerable insights into the mechanism of biotic stress tolerance in plants at the molecular level. Furthermore, different abiotic stress factors may provoke osmotic stress, oxidative stress and protein denaturation in plants, which lead to similar cellular adaptive responses such as accumulation of compatible solutes, induction of stress proteins, and acceleration of reactive oxygen species scavenging systems. Recently, the authores try to improve plant tolerance to salinity injury through either chemical treatments (plant hormones, minerals, amino acids, quaternary ammonium compounds, polyamines and vitamins or biofertilizers treatments (Asymbiotic nitrogen-fixing bacteria, symbiotic nitrogen-fixing bacteria and mycorrhiza or enhanced a process used naturally by plants to minimise the movement of Na+ to the shoot, using genetic modification to amplify the process, helping plants to do what they already do - but to do it much better."

  7. Oral Histoplasmosis.

    Science.gov (United States)

    Folk, Gillian A; Nelson, Brenda L

    2017-02-20

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the disseminated form of histoplasmosis and may present as a fungating or ulcerative lesion of the oral mucosa. The histologic findings and differential diagnosis for oral histoplasmosis are discussed.

  8. Oral leukoplakia

    DEFF Research Database (Denmark)

    Holmstrup, Palle; Dabelsteen, Erik

    2016-01-01

    The idea of identifying oral lesions with a precancerous nature, i.e. in the sense of pertaining to a pathologic process with an increased risk for future malignant development, of course is to prevent frank malignancy to occur in the affected area. The most common oral lesion with a precancerous...... nature is oral leukoplakia, and for decades it has been discussed how to treat these lesions. Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2...

  9. Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.

    Science.gov (United States)

    García-Ara, Carmen; Pedrosa, María; Belver, María Teresa; Martín-Muñoz, María Flor; Quirce, Santiago; Boyano-Martínez, Teresa

    2013-04-01

    Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE 17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    to the political and social relationship between the subject and the objects of toleration. Finally, toleration is often argued to be a normative requirement on the basis of the way it affects the object or receiver of toleration, e.g. on the basis of the good of or right to freedom from non-interference which......The chapter considers how groups might be relevant as objects of policies of toleration and the different senses 'group' might have in relation to questions of toleration. The chapter argues that groups can be relevant to toleration in several different ways as objects of toleration. Toleration...... is routinely defined as involving an objection component, a power requirement and an acceptance component. The objection and acceptance components refer to reasons or dispositions of the subjects of toleration, e.g. public authorities deciding how to act in relation to groups. The power condition refers...

  11. Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis

    NARCIS (Netherlands)

    Stobernack, Tim; Glasner, Corinna; Junker, Sabryna; Gabarrini, Giorgio; de Smit, Menke; de Jong, Anne; Otto, Andreas; Becher, Doerte; van Winkelhoff, Arie Jan; van Dijl, Jan Maarten

    2016-01-01

    Porphyromonas gingivalis is an oral pathogen associated with the inflammatory disease periodontitis. Periodontitis and P. gingivalis have been associated with rheumatoid arthritis. One of the hallmarks of rheumatoid arthritis is the loss of tolerance against citrullinated proteins. Citrullination is

  12. In vivo determination of aluminum, cobalt, chromium, copper, nickel, titanium and vanadium in oral mucosa cells from orthodontic patients with mini-implants by Inductively coupled plasma-mass spectrometry (ICP-MS).

    Science.gov (United States)

    Martín-Cameán, Ana; Jos, Angeles; Puerto, Maria; Calleja, Ana; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

    2015-10-01

    Miniscrews are used as orthodontic anchorage devices in the dentistry clinical practice but the in vivo metallic release from these structures has been not previously investigated. The aim of this study was to determine the content of Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients under orthodontic treatment and with both, orthodontic treatment and miniscrew, in order to know the contribution of these mini-implants to the total metallic content. ICP-MS measurements revealed the following ascending order: Cr

  13. Emerging oral therapies for multiple sclerosis.

    Science.gov (United States)

    Miller, Colleen E; Umhauer, Margaret A

    2011-02-01

    Despite notable advances in the understanding of multiple sclerosis (MS) and the availability of several treatment options, there is a need for therapies that are more effective, safe, convenient, and well tolerated. Several new oral MS therapies are being investigated. Because data on these new therapies continue to emerge, nurses will play a pivotal role in educating patients regarding the benefits and risks of potential treatments and in monitoring patients for response, safety, tolerability, and adherence. This article reviews the oral MS therapies recently approved as well as those currently in development or submitted for Food and Drug Administration approval.

  14. Oral pathology.

    Science.gov (United States)

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  15. Herpes - oral

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000606.htm Herpes - oral To use the sharing features on this page, ... 374. Read More Atopic dermatitis Cancer Fever Genital herpes Mouth ulcers Vesicles Review Date 8/14/2015 Updated ...

  16. Induction machine handbook

    CERN Document Server

    Boldea, Ion

    2002-01-01

    Often called the workhorse of industry, the advent of power electronics and advances in digital control are transforming the induction motor into the racehorse of industrial motion control. Now, the classic texts on induction machines are nearly three decades old, while more recent books on electric motors lack the necessary depth and detail on induction machines.The Induction Machine Handbook fills industry's long-standing need for a comprehensive treatise embracing the many intricate facets of induction machine analysis and design. Moving gradually from simple to complex and from standard to

  17. Role of Combination OF Mifepristone and Misoprostol Verses Misoprostol alone in Induction of Labour in Late Intrauterin Fetal Death: A Prospective Study.

    Directory of Open Access Journals (Sweden)

    Subrat Panda

    2013-12-01

    Full Text Available To compare efficacy, safety and tolerance of combination of mifepristone and misoprostol versus misoprostol-only in induction of late intrauterine fetal death (IUFD.This prospective study included a consecutive series of 52 women gravid up to fourth with IUFD after 28 weeks of gestation between January 2008 and June 2011. Women were divided into two groups. First group of women received a single oral dose of 200mg mifepristone, and after 24 hours, 100ug of intravaginal misoprostol was administered, followed by intravaginal 100µg misoprostol at four hourly intervals if required. Second group of women received 100 µg misoprostol at four hourly interval per vaginally (maximum 600µg in 24 hours. Oxytocin was given for augmentation if needed.The induction-to-delivery time was shorter with the combination regimen (p < 0.001 group. The total dose of misoprostol needed was lower in the group pre-treated with mifepristone (p < 0.001. Oxytocin was required only in misoprostol group. The two groups did not differ as regards complications experienced during labor and delivery significantly.Both regimens, misoprostol-only and the combination of mifepristone and misoprostol are safe in induction of labor after intrauterine fetal death (IUFD. Pre-treatment with mifepristone is more effective in terms of reducing of induction delivery interval, requirement of lesser dose of misoprostol and no need of augmentation with oxytocin.

  18. Disparities in Oral Health

    Science.gov (United States)

    ... 2020: Oral Health Objectives Site Map Disparities in Oral Health Recommend on Facebook Tweet Share Compartir Oral health ... to get and keep dental insurance. Disparities in Oral Health Some of the oral health disparities that exist ...

  19. Lactose tolerance tests

    Science.gov (United States)

    Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen ...

  20. Long term immunologic consequences of experimental stroke and mucosal tolerance

    Directory of Open Access Journals (Sweden)

    Gee J Michael

    2009-10-01

    Full Text Available Abstract Background An inflammatory insult following middle cerebral artery occlusion (MCAO is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP. Induction of immunologic tolerance to brain antigens prior to MCAO prevents this deleterious autoimmune response and is associated with better functional outcome early after stroke. In this study, we sought to determine the long term immunologic consequences of experimental stroke and induction of mucosal tolerance. Methods Male Lewis rats were tolerized to MBP or ovalbumin (OVA by intranasal administration prior to MCAO and administration of lipopolysaccharide (LPS. Neurological outcome was assessed at set points after MCAO and animals sacrificed at 3 months; the immune response to MBP in brain and spleen was determined using ELISPOT assay and degree of cellular inflammatory brain infiltrate assessed by immunocytochemistry. Results Animals that developed a pro-inflammatory (TH1 response to MBP experienced worse outcome, while those that developed a regulatory response (TREG experienced better outcome. A TREG response in spleen was also associated with decreased inflammation and an increase in the number of FoxP3 positive cells in brain. In this study, tolerization to MBP prior to MCAO was associated with a tendency to develop a TH1 response to MBP by 3 months after MCAO. Conclusion These data show that induction of immunological tolerance to MBP is associated with improved outcome after stroke. This study, however, raises concern about the potential for inadvertent induction of detrimental autoimmunity through mucosal administration of antigen.

  1. Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Alabsi, Aied M; Lim, Kai Li; Paterson, Ian C; Ali-Saeed, Rola; Muharram, Bushra A

    2016-01-01

    Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

  2. Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Aied M. Alabsi

    2016-01-01

    Full Text Available Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC. The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

  3. 77 FR 68692 - 1,4-Dimethylnaphthalene; Amendment to an Exemption From the Requirement of a Tolerance

    Science.gov (United States)

    2012-11-16

    ... 1,4-DMN to support the expansion of the tolerance exemption. 1,4-DMN was administered by oral gavage... mating performance, fertility, fecundity, litter survival, sperm morphology/vaginal cytology as well as... (150 ppm) for females. The previous tolerance exemption showed an acute oral toxicity LD 50 of 2,730...

  4. Gestational weight gain and pregnancy outcomes in 481 obese glucose-tolerant women

    DEFF Research Database (Denmark)

    Jensen, Dorte Møller; Ovesen, Per; Beck-Nielsen, Henning

    2005-01-01

    .0-11.0]). There was no difference in rates of small-for-gestational-age infants. Significant predictors for birth weight (determined by multiple linear regression) were gestational weight gain, 2-h OGTT result, pre-gestational BMI, maternal age, gestational age, and smoking. CONCLUSIONS: Increasing weight gain in obese women......OBJECTIVE: To investigate the effect of gestational weight gain in obese glucose-tolerant women. RESEARCH DESIGN AND METHODS: We performed a historical cohort study of 481 women with prepregnancy BMI > or = 30 kg/m2 and a normal 2-h 75-g oral glucose tolerance test (OGTT) during the third trimester......-weight women (3,478 g). In multivariate analyses, increasing weight gain was associated with significantly higher rates of hypertension (OR 4.8 [95% CI for group 4 vs. group 1: 1.7-13.1]), cesarean section (3.5 [1.6-7.8]), induction of labor (3.7 [1.7-8.0]), and large-for-gestational-age infants (4.7 [2...

  5. Assessing oral bioaccessibility of trace elements in soils under worst-case scenarios by automated in-line dynamic extraction as a front end to inductively coupled plasma atomic emission spectrometry.

    Science.gov (United States)

    Rosende, María; Magalhães, Luis M; Segundo, Marcela A; Miró, Manuel

    2014-09-01

    A novel biomimetic extraction procedure that allows for the in-line handing of ≥400 mg solid substrates is herein proposed for automatic ascertainment of trace element (TE) bioaccessibility in soils under worst-case conditions as per recommendations of ISO norms. A unified bioaccessibility/BARGE method (UBM)-like physiological-based extraction test is evaluated for the first time in a dynamic format for accurate assessment of in-vitro bioaccessibility of Cr, Cu, Ni, Pb and Zn in forest and residential-garden soils by on-line coupling of a hybrid flow set-up to inductively coupled plasma atomic emission spectrometry. Three biologically relevant operational extraction modes mimicking: (i) gastric juice extraction alone; (ii) saliva and gastric juice composite in unidirectional flow extraction format and (iii) saliva and gastric juice composite in a recirculation mode were thoroughly investigated. The extraction profiles of the three configurations using digestive fluids were proven to fit a first order reaction kinetic model for estimating the maximum TE bioaccessibility, that is, the actual worst-case scenario in human risk assessment protocols. A full factorial design, in which the sample amount (400-800 mg), the extractant flow rate (0.5-1.5 mL min(-1)) and the extraction temperature (27-37°C) were selected as variables for the multivariate optimization studies in order to obtain the maximum TE extractability. Two soils of varied physicochemical properties were analysed and no significant differences were found at the 0.05 significance level between the summation of leached concentrations of TE in gastric juice plus the residual fraction and the total concentration of the overall assayed metals determined by microwave digestion. These results showed the reliability and lack of bias (trueness) of the automatic biomimetic extraction approach using digestive juices.

  6. Open, multicenter comparison of efficacy, cycle control, and tolerability of a 23-day oral contraceptive regimen with 20 microg ethinyl estradiol and 75 microg gestodene and a 21-day regimen with 20 microg ethinyl estradiol and 150 microg desogestrel.

    Science.gov (United States)

    Endrikat, J; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

    2001-09-01

    This prospective, open, randomized study was conducted to compare the contraceptive reliability, cycle control, and tolerability of a 23-day regimen with 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) and a 21-day regimen with 20 microg EE and 150 microg desogestrel (DSG). Participants took either 23 tablets with active substances plus 5 placebo tablets (23-day EE/GSD) or 21 tablets with active substances followed by 7 days without pill-taking (21-day EE/DSG). Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of seven cycles. Efficacy data gathered from 5967 treatment cycles (23-day EE/GSD: 2975 cycles; 21-day EE/DSG: 2992 cycles) were obtained from 890 participants (445 in each group). Both preparations proved to be effective contraceptives and provided good cycle control. No pregnancy during treatment was recorded. This resulted in a study Pearl Index of 0.0 for both treatments. For 23-day EE/GSD, 32.4% of participants reported at least one intracyclic bleeding episode during Cycles 2-4 (primary target) compared to 31.5% for 21-day EE/DSG. In the 23-day EE/GSD group, intracyclic bleeding episodes were reported by 48.8% of the participants in Cycle 1 but in only 15.1% in Cycle 7, and in the 21-day regimen group by 43.4% in Cycle 1 and only 14.2% in Cycle 7. Overall, intracyclic bleeding was reported in 20.9% of cycles for both treatments.A greater number of 23-day EE/GSD participants had shorter withdrawal bleeding periods than with 21-day EE/DSG. In significantly (p <0.0001) more cycles in the 23-day EE/GSD group participants reported withdrawal bleeding periods that lasted only 1-4 days compared to the 21-day EE/DSG group. For the majority of the treatment cycles, the median number of bleeding days in the 23-day EE/GSD group was 4 days and in the 21-day EE/DSG group 5 days. Both preparations were well tolerated and showed a similar adverse events pattern. The discontinuation rate because of adverse events was

  7. Oral candidiasis.

    Science.gov (United States)

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options.

  8. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2010-01-01

    Full Text Available Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

  9. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

  10. Prevention of house dust mite induced allergic airways disease in mice through immune tolerance.

    Science.gov (United States)

    Agua-Doce, Ana; Graca, Luis

    2011-01-01

    Allergic airways disease is a consequence of a Th2 response to an allergen leading to a series of manifestations such as production of allergen-specific IgE, inflammatory infiltrates in the airways, and airway hyper-reactivity (AHR). Several strategies have been reported for tolerance induction to allergens leading to protection from allergic airways disease. We now show that CD4 blockade at the time of house dust mite sensitization induces antigen-specific tolerance in mice. Tolerance induction is robust enough to be effective in pre-sensitized animals, even in those where AHR was pre-established. Tolerant mice are protected from airways eosinophilia, Th2 lung infiltration, and AHR. Furthermore, anti-CD4 treated mice remain immune competent to mount immune responses, including Th2, to unrelated antigens. Our findings, therefore, describe a strategy for tolerance induction potentially applicable to other immunogenic proteins besides allergens.

  11. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2004-01-01

    BackgroundDimensioning and TolerancingTolerance Format and Decimal PlacesConverting Plus/Minus Dimensions and Tolerances into Equal Bilaterally Toleranced DimensionsVariation and Sources of VariationTolerance AnalysisWorst-case Tolerance StackupsStatistical Tolerance StackupsGeometric Dimensioning and Tolerancing (GD&T)Converting Plus/Minus Tolerancing to Positional Tolerancing and Projected Tolerance ZonesDiametral and Radial Tolerance StackupsSpecifying Material Condition Modifiers and Their Effect on Tolerance Stackups The Tolerance Stackup SketchThe Tolerance Stackup Report FormTolerance S

  12. Compromise and Toleration

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...... respecting the plurality of conceptions of the good in society, whereas political compromise embodies the disagreements in coercive laws. This difference between toleration and compromise has two important consequences. First, political compromise is justified in a different manner than is toleration...

  13. A COMPARATIVE STUDY BETWEEN ORAL CLONIDINE AND ORAL MIDAZOLAM AS PREMEDICANT IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Gurudatta

    2015-08-01

    Full Text Available Majority of Paediatric patients experience significant anxiety in the preoperative holding area and during induction of anesthesia. Such anxiety often prolongs the induction of Anesthesia, increases post - operative pain and produces negative behavioral changes in chil dren. Effective premedication is the answer, which permits less traumatic separation of child from parents and facilitates smooth induction of anesthesia. The aim of the study is to evaluate and compare the efficacy of oral clonidine v/s oral midazolam adm inistered as a pre medicant in children. METHODS: 100 patients of ASA group I/II of either sex between the age group 4 years to 12 years scheduled for elective surgery were divided into two groups. (1 Group C received tablet oral clonidine 4μg/kg mixed wi th 5 ml of water 90 minutes before the induction. (2 Group M – received oral midazolam syrup 0.5mg/kg 45 minutes before the induction. Both the groups were assessed for: (1 drug acceptance (2 sedation score (3 anxiety score (4 onset of sedation (5 ma sk acceptance (6 Cardio respiratory scoring (7 OPS scoring (8 Parental acceptance. The results were statistically analysed. CONCLUSION: Premedication with oral clonidine is a suitable alternative to oral midazolam. It has several advantages compared to oral midazolam, like better acceptance of the drug by the children, adequate sedation and anxiolysis, easy acceptance of mask and I.V. cannulation, minimal side effects, adequate analgesia, good parental satisfaction. One disadvantage of clonidine is slowe r onset of action

  14. Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial.

    Science.gov (United States)

    Pratzel, H G; Alken, R G; Ramm, S

    1996-10-01

    The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial. A total of 138 patients, aged between 20 and 75 years, with painful reflex muscle spasm associated with diseases of the spinal column or proximal joints were enrolled in eight rehabilitation centers. Patients were randomized to receive either 300 mg tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment. The overall assessment of efficacy by the patient also demonstrated significant differences in favor of tolperisone hydrochloride. Best results were seen in patients aged between 40 and 60 years with a history of complaints shorter than 1 year and with concomitant physical therapy. The evaluation of safety data, i.e., adverse events, biochemical and hematological laboratory parameters, demonstrated no differences between tolperisone hydrochloride and placebo. As a conclusion tolperisone hydrochloride represents an effective and safe treatment of painful reflex muscle spasm without the typical side effects of centrally active muscle relaxants.

  15. Fully integrated wireless inductive tongue computer interface for disabled people.

    Science.gov (United States)

    Struijk, Lotte N S Andreasen; Lontis, Eugen Romulus; Bentsen, Bo; Christensen, Henrik Vie; Caltenco, Hector A; Lund