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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of infectious diseases, 01 July 2012, Vol.206(1), pp.135-9
    Description: Infections due to mucormycetes have a poor outcome, in particular in allogeneic hematopoietic stem cell transplantation (HSCT). In order to evaluate the cellular host response against mucormycetes, we enriched and cultivated anti-Rhizopus oryzae T cells from healthy individuals. These cells were characterized as memory/effector T(H)1 cells, they proliferated upon restimulation, they exhibited cross-reactivity to some but not all Mucorales species tested, and they increased the activity of phagocytes. Compared with the original cell fraction, the generated cells exhibited significant lower alloreactivity. Our data may form the basis for further investigations, which may ultimately lead to adoptive immunotherapeutic strategies for allogeneic HSCT recipients suffering from mucormycosis.
    Keywords: Hematopoietic Stem Cell Transplantation ; Immunity, Cellular -- Immunology ; Rhizopus -- Immunology ; Th1 Cells -- Immunology
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: Antimicrobial agents and chemotherapy, February 2019, Vol.63(2)
    Description: Despite the availability of new antifungal compounds, invasive aspergillosis carries high morbidity and mortality in hematopoietic stem cell transplant recipients. studies and animal models suggest that the adoptive transfer of natural killer (NK) cells might be a promising immunotherapeutic option in this setting. As it is unclear whether the viability and function of human NK cells are affected by common antifungal agents, we analyzed the interaction of various concentrations of amphotericin B deoxycholate (AmB-D), liposomal amphotericin B, caspofungin, fluconazole, voriconazole, and posaconazole with human NK cells. When adding NK cells to therapeutic concentrations of antifungal agents, a significant increase in the antifungal effect was seen for caspofungin and voriconazole, whereas NK cells significantly decreased the hyphal damage of escalated doses of AmB-D. In contrast, therapeutic concentrations of all antifungal compounds tested did not have a negative effect on proliferation, viability, and the release of soluble immunomodulatory molecules of NK cells. These data indicate that therapeutic concentrations of the antifungal agents tested do not negatively affect the functional properties of human NK cells, which is a prerequisite for further studies evaluating NK cells as antifungal immunotherapy in immunocompromised patients suffering from invasive aspergillosis.
    Keywords: Aspergillus Fumigatus ; Antifungal Agent ; Human Natural Killer Cell
    ISSN: 00664804
    E-ISSN: 1098-6596
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  • 3
    Language: English
    In: Nutrition, November 2016, Vol.32(11-12), pp.1165-1170
    Description: Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil–associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil–derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies. In addition to immune-controlling prostaglandins, leukotrienes, and thromboxanes, specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, are metabolized from different LCPUFA, which actively resolve inflammation. The aim of this review was to discuss the possible synergistic effects of ω-3 and ω-6 LCPUFA combinations concerning rebuilding fatty acid homeostasis in cellular membranes, modifying eicosanoid metabolic pathways, controlling inflammatory processes by focusing on resolving inflammation in the bronchoalveolar system on the cellular level, and helping to control clinical symptoms in bronchial asthma.
    Keywords: Arachidonic Acid ; Allergic Disease ; Eicosapentaenoic Acid ; Fat Metabolism ; Inflammation ; Pulmonology ; Anatomy & Physiology ; Diet & Clinical Nutrition
    ISSN: 0899-9007
    E-ISSN: 1873-1244
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  • 4
    In: PLoS ONE, 2016, Vol.11(6)
    Description: Objective Mucoactive drugs should increase the ability to expectorate sputum and, ideally, have anti-inflammatory properties. The aim of the study was to evaluate the mucolytic activity of Tyloxapol compared to saline (0.9%) in COPD. Design A randomized, placebo-controlled, double-blinded crossover, clinical trial was carried out. Patients were randomly assigned to either inhale 5 ml Tyloxapol 1% or saline 0.9% solution three times daily for 3 weeks and vice versa for another 3 weeks. 28 patients (18 male, 10 female, 47 to 73 years old, median age 63.50) were screened, 21 were treated and 19 patients completed the study per protocol. Results A comparison of the two treatment phases showed that the primary endpoint sputum weight was statistically significant higher when patients inhaled Tyloxapol (mean 4.03 g, 95% CI: 2.34–5.73 g at week 3) compared to saline (mean 2.63 g, 95% CI: 1.73–3.53 g at week 3). The p-value at three weeks of treatment was 0.041 between treatment arms. Sputum cells decreased during the Tyloxapol treatment after 3 weeks, indicating that Tyloxapol might have some anti-neutrophilic properties. Lung function parameters (FVC, FEV 1 , RV, and RV/TLC) remained stable during the study, and no treatment effect was shown. Interestingly, there was a mean increase in all inflammatory cytokines (IL-1β, IL-6, and IL-8) during the saline treatment from day 1 to week 3, whereas during the Tyloxapol treatment, all cytokines decreased. Due to the small sample size and the large individual variation in sputum cytokines, these differences were not significant. However, analyses confirmed that Tyloxapol has significant anti-inflammatory properties in vitro. Despite the high number of inhalations (more than 1000), only 27 adverse events (20 during the Tyloxapol and seven during saline) were recorded. Eleven patients experienced AEs under Tyloxapol and six under saline treatment, which indicates that inhalation of saline or Tyloxapol is a very safe procedure. Conclusion Our study demonstrated that inhalation of Tyloxapol by patients with COPD is safe and superior to saline and has some anti-inflammatory effects. Trial Registration ClinicalTrials.gov NCT02515799
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(2), p.e0171249
    Description: BACKGROUND:Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. METHODS:In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. RESULTS:DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p〈 0.05). CONCLUSIONS:SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients and may serve as a representative peripheral biomarker of the lung resolution program for CF patients.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: BMC Complementary and Alternative Medicine, June 3, 2011, Vol.11, p.45
    Description: Background Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, ?-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. Trial registration EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT00677209
    Keywords: Immune Response -- Research ; Asthma -- Diagnosis ; Asthma -- Care And Treatment ; Asthma -- Research ; Escherichia Coli -- Health Aspects ; Escherichia Coli -- Research
    ISSN: 1472-6882
    Source: Cengage Learning, Inc.
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  • 7
    Language: English
    In: BMC Complementary and Alternative Medicine, June 3, 2011, Vol.11, p.45
    Description: Background Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, ?-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. Trial registration EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT00677209
    Keywords: Immune Response -- Research ; Asthma -- Diagnosis ; Asthma -- Care And Treatment ; Asthma -- Research ; Escherichia Coli -- Health Aspects ; Escherichia Coli -- Research
    ISSN: 1472-6882
    Source: Cengage Learning, Inc.
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  • 8
    Language: English
    In: Journal of Neurogenetics, 01 October 2011, Vol.25(3), pp.78-81
    Description: Ataxia-telangiectasia (A-T) is a devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. The European Workshop on Ataxia-Telangiectasia 2011 in Frankfurt focused on status quo of patient care and future...
    Keywords: Ataxia-Telangiectasia (A-T) ; A-T Advocacy Organizations ; A-T Registry ; Cancer ; Chromosomal Instability ; Immunodeficiency ; Anatomy & Physiology
    ISSN: 0167-7063
    E-ISSN: 1563-5260
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  • 9
    Language: English
    In: BMC Complementary and Alternative Medicine, 01 June 2011, Vol.11(1), p.45
    Description: Abstract Background Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p = 0.334) compared to initial values (from 32.6 to 42.2 ppb; p = 0.046) (p = 0.034). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, Β-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. Trial registration EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID 〈a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=677209"〉NCT00677209〈/a〉
    Keywords: Autovaccine ; Safety ; Tolerability ; House Dust Mite Allergy ; Asthma ; Medicine
    ISSN: 1472-6882
    E-ISSN: 1472-6882
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  • 10
    Language: English
    In: Nutrition, May 2018, Vol.49, pp.66-73
    Description: On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D ) levels and immune cells including T helper cells (Th; CD3 CD4 ), late-activated Th cells (CD3 CD4 HLA-DR ), regulatory T cells (CD3 CD4 CD25 CD127 ), cytotoxic T cells (Tc; CD3 CD8 ), late-activated Tc cells (CD3 CD8 HLA-DR ), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Ten of 13 patients (77%) were VD deficient. Median 25(OH)D concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml;  = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%;  = 0.02) and late-activated Tc cells (median changes: 4.05%;  = 0.03) decreased, whereas monocytes (median changes: 1.05%;  = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms ( and ), but no changes in the 21-hydroxylase antibody titers were observed. Three months of treatment with cholecalciferol achieved sufficient 25(OH)D levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD.
    Keywords: Adrenal Insufficiency ; Immune Cells ; Cholecalciferol ; Therapy ; Cross-Over Trial ; 25(Oh)D3 Levels ; Genetic Profiling ; Anatomy & Physiology ; Diet & Clinical Nutrition
    ISSN: 0899-9007
    E-ISSN: 1873-1244
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