413 research outputs found
Modulation of asthma and allergy by addressing toll-like receptor 2
Toll-like receptors play an important role in innate and adaptive immunity and in balancing immune responses with tolerance. TLR2 is related to protection against allergies and allergic asthma by sensing pathogen associated patterns as lipoproteins and lipopeptides. A constant Th1 triggering is thought to prevent Th2 related disorders
Pharmacokinetics of recombinant human erythropoietin applied subcutaneously to children with chronic renal failure
The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEPO) given SC was investigated in 20 patients aged 7-20 years at different stages of chronic renal failure. In a pilot study we confirmed the lower bioavailability of the drug in 2 children when given SC compared with the IV route (24% and 43%, respectively). Following administration of 4,000 units/m2, rHuEPO SC effective serum erythropoietin concentrations increased from a mean baseline level (+/- SD) of 23 +/- 13 units/l to a mean peak concentration of 265 +/- 123 units/l, which was reached after 14.3 +/- 9.4 h, followed by a slow decline until baseline values were attained at 72 h. Mean residence time was 30 +/- 9 h and mean elimination half-time 14.3 +/- 7 h. The single-dose kinetics of SC rHuEPO in children with different degrees of renal failure are comparable to those in adult patients. Possibly, the higher efficacy of SC rHuEPO in patients with renal anaemia compared with IV rHuEPO is related to its prolonged action
The Sequence of Events generator: A powerful tool for mission operations
The functions and features of the sequence of events (SOE) and flight operations procedures (FOP) generator developed and used at DLR/GSOC for the positioning of EUTELSAT 2 satellites are presented. The SOE and FOP are the main operational documents that are prepared for nominal as well as for non-nominal mission execution. Their structure and application are described. Both of these documents are generated, validated, and maintained by a common software tool. Its main features and advantages are demonstrated. The tool has been improved continuously over the last 5 years. Due to its flexibility it can easily be applied to other projects and new features may be added
Expression of VPAC1 in a murine model of allergic asthma
Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter of the inhibitory non-adrenergic non-cholinergic nervous system and influences the mammalian airway function in various ways. Hence known for bronchodilatory, immunomodulatory and mucus secretion modulating effects by interacting with the VIP receptors VPAC1 and VPAC2, it is discussed to be a promising target for pharmaceutical intervention in common diseases such as COPD and bronchial asthma. Here we examined the expression and transcriptional regulation of VPAC1 in the lungs of allergic mice using an ovalbumin (OVA) -induced model of allergic asthma. Mice were sensitized to OVA and challenged with an OVA aerosol. In parallel a control group was sham sensitized with saline. VPAC1 expression was examined using RT-PCR and real time-PCR studies were performed to quantify gene transcription. VPAC1 mRNA expression was detected in all samples of OVA-sensitized and challenged animals and control tissues. Further realtime analysis did not show significant differences at the transcriptional level.
Although the present studies did not indicate a major transcriptional regulation of VPAC1 in states of allergic airway inflammation, immunomodulatory effects of VPAC1 might still be present due to regulations at the translational level
PERFORMANCE GAINS IN RELAY SWIMMING (PART I): THE RELAY START BENEFIT COMPONENT
The present study aimed to detect statistical differences in the start performance between relay and individual races accounting for gender and relay start techniques. Race data of relay races and corresponding individual races from European Championships (2019) were analysed. Linear mixed models for repeated measures were applied to compare the differences in the 15 m start times (after toe-off) between relay and individual races accounting for gender and relay start techniques. The results revealed a small time benefit for step-starts over no-step starts in the freestyle races. Furthermore, depending on techniques, male butterfly swimmers showed more pronounced differences in their start performance as compared to female swimmers. However, no statistical differences were found in breaststroke races for either gender or relay start technique. The findings of the present study may improve coaches\u27 and swimmers\u27 understanding of the downsides and benefits of different relay starts. Based on results, we suggest that, at least for freestyle relays, a step-start should be the relay start technique of choice
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Surface defects reduce Carbon Nanotube toxicity in vitro
The cytotoxicity of two different types of Multi-walled Carbon Nanotubes (MWCNTs)in A549 lung epithelial cells and HepG2 hepatocytes was investigated. One MWCNT still contained iron that was used as a catalyst during production, while the other one had all iron removed in a post-production heat treatment resulting in significantly fewer surface defects. The WST-8 assay was applied to test cell viability. To check the integrity of the cell membrane, we performed the lactate dehydrogenases assay (LDH)and measured the cellular production of reactive oxygen species (ROS). Finally, to examine cell proliferation, we conducted a cell cycle analysis. The results showed a dose- and time-dependent decrease in cell viability for both MWCNTs in both cell types. Moreover, a dose- and time-dependent increase in LDH leakage was detected, thereby indicating a decreased membrane integrity. The production of ROS was significantly increased in the case of the heat-treated MWCNTs. The heat-treated MWCNTs showed significantly stronger adverse effects when compared to the non-treated MWCNTs. Additionally, the heat-treated MWCNTs induced a dose-dependent cell cycle arrest in A549 cells. Both MWCNTs induced a significant cytotoxicity, whereby the heat treatment, leading to a decrease in surface defects, further increased the indicated adverse effects. © 2019 The Author
From Cancer to Immune-Mediated Diseases and Tolerance Induction: Lessons Learned From Immune Oncology and Classical Anti-cancer Treatment
Success in cancer treatment over the last four decades has ranged from improvements
in classical drug therapy to immune oncology. Anti-cancer drugs have also often proven
beneficial for the treatment of inflammatory and autoimmune diseases. In this review,
we report on challenging examples that bridge between treatment of cancer and
immune-mediated diseases, addressing mechanisms and experimental models as well
as clinical investigations. Patient-derived tumor xenograft (PDX) (humanized) mouse
models represent useful tools for preclinical evaluation of new therapies and biomarker
identification. However, new developments using human ex vivo approaches modeling
cancer, for example in microfluidic human organs-on-chips, promise to identify key
molecular, cellular and immunological features of human cancer progression in a fully
human setting. Classical drugs which bridge the gap, for instance, include cytotoxic
drugs, proteasome inhibitors, PI3K/mTOR inhibitors and metabolic inhibitors. Biologicals
developed for cancer therapy have also shown efficacy in the treatment of autoimmune
diseases. In immune oncology, redirected chimeric antigen receptor (CAR) T cells have
achieved spectacular remissions in refractory B cell leukemia and lymphoma and are
currently under development for tolerance induction using cell-based therapies such as
CAR Tregs or NK cells. Finally, a brief outline will be given of the lessons learned from
bridging cancer and autoimmune diseases as well as tolerance induction
Effects of ultrafine particles on the allergic inflammation in the lung of asthmatics : results of a double-blinded randomized cross-over clinical pilot study
Background: Epidemiological and experimental studies suggest that exposure to ultrafine particles (UFP) might aggravate the allergic inflammation of the lung in asthmatics.
Methods: We exposed 12 allergic asthmatics in two subgroups in a double-blinded randomized cross-over design, first to freshly generated ultrafine carbon particles (64 μg/m3; 6.1 ± 0.4 × 105 particles/cm3 for 2 h) and then to filtered air or vice versa with a 28-day recovery period in-between. Eighteen hours after each exposure, grass pollen was instilled into a lung lobe via bronchoscopy. Another 24 hours later, inflammatory cells were collected by means of bronchoalveolar lavage (BAL). (Trial registration: NCT00527462)
Results: For the entire study group, inhalation of UFP by itself had no significant effect on the allergen induced
inflammatory response measured with total cell count as compared to exposure with filtered air (p = 0.188). However, the subgroup of subjects, which inhaled UFP during the first exposure, exhibited a significant increase in total BAL cells (p = 0.021), eosinophils (p = 0.031) and monocytes (p = 0.013) after filtered air exposure and subsequent allergen challenge 28 days later. Additionally, the potential of BAL cells to generate oxidant radicals was
significantly elevated at that time point. The subgroup that was exposed first to filtered air and 28 days later to UFP did not reveal differences between sessions.
Conclusions: Our data demonstrate that pre-allergen exposure to UFP had no acute effect on the allergic inflammation. However, the subgroup analysis lead to the speculation that inhaled UFP particles might have a long-term effect on the inflammatory course in asthmatic patients. This should be reconfirmed in further studies with an appropriate study design and sufficient number of subjects
Invasive versus noninvasive measurement of allergic and cholinergic airway responsiveness in mice
BACKGROUND: This study seeks to compare the ability of repeatable invasive and noninvasive lung function methods to assess allergen-specific and cholinergic airway responsiveness (AR) in intact, spontaneously breathing BALB/c mice. METHODS: Using noninvasive head-out body plethysmography and the decrease in tidal midexpiratory flow (EF(50)), we determined early AR (EAR) to inhaled Aspergillus fumigatus antigens in conscious mice. These measurements were paralleled by invasive determination of pulmonary conductance (GL), dynamic compliance (Cdyn) and EF(50 )in another group of anesthetized, orotracheally intubated mice. RESULTS: With both methods, allergic mice, sensitized and boosted with A. fumigatus, elicited allergen-specific EAR to A. fumigatus (p < 0.05 versus controls). Dose-response studies to aerosolized methacholine (MCh) were performed in the same animals 48 h later, showing that allergic mice relative to controls were distinctly more responsive (p < 0.05) and revealed acute airway inflammation as evidenced from increased eosinophils and lymphocytes in bronchoalveolar lavage. CONCLUSION: We conclude that invasive and noninvasive pulmonary function tests are capable of detecting both allergen-specific and cholinergic AR in intact, allergic mice. The invasive determination of GL and Cdyn is superior in sensitivity, whereas the noninvasive EF(50 )method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of conscious mice
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