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  • PMC (PubMed Central)  (14)
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  • 1
    Language: English
    In: Sci Rep, 2017, Vol.7(1), pp.8288-8288
    Description: Herbivory and disturbance are major drivers of biological invasions, but it is unclear how they interact to determine exotic vs. native seedling recruitment and what consequences arise for biodiversity and ecosystem functioning. Previous studies neglected the roles of different, potentially interacting, guilds of generalist herbivores such as rodents and gastropods. We therefore set up a full-factorial rodent exclusion x gastropod exclusion x disturbance x seed-addition experiment in a grassland community in Central Germany and measured early seedling recruitment, as well as species richness, species composition and aboveground biomass. Gastropod herbivory reduced the positive effect of disturbance on seedling recruitment, particularly for exotic species. Rodent herbivory had weak positive effects on seedling recruitment at undisturbed sites, irrespective of species origin. This effect was likely driven by their strong negative effect on productivity. Interactive effects between both herbivore guilds became only evident for species richness and composition. How many species established themselves depended on disturbance, but was independent of species origin. The fewer exotic species that established themselves increased productivity to a stronger extent compared to native species. Our study highlights that joint effects of disturbance, herbivory and species origin shape early recruitment, while they only weakly affect biodiversity and ecosystem functioning.
    Keywords: Article;
    ISSN: 2045-2322
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  • 2
    Language: English
    In: The Journal of Allergy and Clinical Immunology, August 2017, Vol.140(2), pp.525-533.e10
    Description: Allergy vaccines should be easily applicable, safe, and efficacious. For Bet v 1–mediated birch pollen and associated food allergies, a single wild-type allergen does not provide a complete solution. We aimed to combine immunologically relevant epitopes of Bet v 1 and the 2 clinically most important related food allergens from apple and hazelnut to a single hybrid protein, termed MBC4. After identification of T cell epitope–containing parts on each of the 3 parental allergens, the hybrid molecule was designed to cover relevant epitopes and evaluated . Thereby a mutation was introduced into the hybrid sequence, which should alter the secondary structure without compromising the immunogenic properties of the molecule. MBC4 and the parental allergens were purified to homogeneity. Analyses of secondary structure elements revealed substantial changes rendering the hybrid nonreactive with patients' serum IgE. Nevertheless, the protein was monomeric in solution. MBC4 was able to activate T-cell lines from donors with birch pollen allergy and from mice immunized with the parental allergens. Moreover, on immunization of mice and rabbits, MBC4 induced cross-reactive IgG antibodies, which were able to block the binding of human serum IgE. Directed epitope rearrangements combined with a knowledge-based structural modification resulted in a protein unable to bind IgE from allergic patients. Still, properties to activate specific T cells or induce blocking antibodies were conserved. This suggests that MBC4 is a suitable vaccine candidate for the simultaneous treatment of Bet v 1 and associated food allergies.
    Keywords: Birch Pollen Allergy ; Bet V 1 ; Birch Pollen–Associated Food Allergy ; Allergy Vaccine Candidate ; Molecular Allergology ; Medicine
    ISSN: 0091-6749
    E-ISSN: 1097-6825
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(7), p.e0132810
    Description: Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperoxia may attenuate this effect. Immediately after blast wave-induced blunt chest trauma, mice (n=32) with or without 3-4 weeks of CS exposure underwent 4 hours of pressure-controlled, thoraco-pulmonary compliance-titrated, lung-protective mechanical ventilation with air or 100% O2. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1 (HO-1), activated caspase-3, and hypoxia-inducible factor 1-α (HIF-1α) expression, nuclear factor-κB (NF-κB) activation, nitrotyrosine formation, purinergic receptor 2X4 (P2XR4) and 2X7 (P2XR7) expression, and histological scoring. CS exposure prior to chest trauma lead to higher pulmonary compliance and lower PaO2 and Horovitz-index, associated with increased tissue IL-18 and blood MCP-1 concentrations, a 2-4-fold higher inflammatory cell infiltration, and more pronounced alveolar membrane thickening. This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression. Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice. However, hyperoxia attenuated tissue HIF-1α, nitrotyrosine, P2XR7, and P2XR4 expression, while it increased HO-1 formation in CS exposed mice. Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Psychopharmacology, 2010, Vol.208(3), pp.353-363
    Description: Rationale/objectives: There is a high prevalence of substance use disorder (SUD) in first-episode schizophrenia (SZ), but its contribution to the underlying SZ pathophysiology remains unclear. Several studies using transcranial magnetic stimulation (TMS) have observed abnormalities in human motor cortex (M1) excitability in SZ. Studies on cortical excitability comparing SZ patients with and without comorbid substance abuse are lacking. Methods: A total of 29 first-episode SZ patients participated in this study; 12 had a history of comorbid cannabis abuse (SZ-SUD) and 17 did not (SZ-NSUD). We applied TMS to right and left M1 areas to assess the resting motor threshold (RMT), short-interval cortical inhibition (SICI), intracortical facilitation (ICF), and the contralateral cortical silent period (CSP). Results: In SICI and ICF conditions, right M1 stimulation led to significantly higher motor evoked potential ratios in SZ-SUD compared to SZ-NSUD. This suggests lower cortical inhibition and increased ICF in first-episode SZ with previous cannabis abuse. There were no group differences in RMT and CSP duration. Neither were there any significant correlations between psychopathology (as indexed by Positive and Negative Syndrome Scale), disease characteristics, the extent of cannabis abuse, and TMS parameters (SICI, ICF, and CSP). Conclusions: Comorbid cannabis abuse may potentiate the reduced intracortical inhibition and enhanced ICF observed in first-episode SZ patients in some previous studies. This finding suggests an increased alteration of GABA sub(A) and NMDA receptor activity in cannabis-abusing first-episode patients as compared to schizophrenia patients with no history of substance abuse. This may constitute a distinct vulnerability factor in this special population.
    Keywords: Schizophrenia ; Substance abuse ; Cortical inhibition ; Transcranial magnetic stimulation (TMS) ; Cannabinoids ; Electrophysiology
    ISSN: 0033-3158
    E-ISSN: 1432-2072
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  • 5
    Language: English
    In: BMC Anesthesiology, 01 December 2010, Vol.10(1), p.22
    Description: Abstract Background It has never been specified how many of the extended general and inflammatory variables of the 2003 SCCM/ESICM/ACCP/ATS/SIS consensus sepsis definitions are mandatory to define sepsis. Objectives To find out how many of these variables are needed to identify almost all patients with septic shock. Methods Retrospective observational single-centre study in postoperative/posttraumatic patients admitted to an University adult ICU. The survey looked at 1355 admissions, from 01/2007 to 12/2008, that were monitored daily computer-assisted for the eight general and inflammatory variables temperature, heart rate, respiratory rate, significant edema, positive fluid balance, hyperglycemia, white blood cell count and C-reactive protein. A total of 507 patients with infections were classified based on the first day with the highest diagnostic category of sepsis during their stay using a cut-off of 1/8 variables compared with the corresponding classification based on a cut-off of 2, 3, 4, 5, 6, 7 or 8/8 variables. Results Applying cut-offs of 1/8 up to 8/8 variables resulted in a decreased detection rate of cases with septic shock, i.e., from 106, 105, 103, 93, 65, 21, 3 to 0. The mortality rate increased up to a cut-off of 6/8 variables, i.e., 31% (33/106), 31% (33/105), 31% (32/103), 32% (30/93), 38% (25/65), 43% (9/21), 33% (1/3) and 0% (0/0). Conclusions Frequencies and mortality rates of diagnostic categories of sepsis differ depending on the cut-off for general and inflammatory variables. A cut-off of 3/8 variables is needed to identify almost all patients with septic shock who may benefit from optimal treatment.
    Keywords: Research Article;
    ISSN: 1471-2253
    E-ISSN: 1471-2253
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  • 6
    Language: English
    In: Clinical Research in Cardiology, 2016, Vol.105(4), pp.349-355
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00392-015-0927-z Byline: Eva-Luise Hobl (1), Birgit Reiter (2), Christian Schoergenhofer (1), Michael Schwameis (1), Ulla Derhaschnig (1), Irene Marthe Lang (3), Thomas Stimpfl (2), Bernd Jilma (1) Keywords: Drug interactions; Morphine; Platelet function tests; Prasugrel; Vasodilator-stimulated phosphoprotein Abstract: Background Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction. Objectives To clarify whether more potent P2Y.sub.12-inhibitors may provide an effective alternative, we examined drug--drug interactions between morphine and prasugrel. Methods Twelve healthy volunteers received 60 mg prasugrel with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and prasugrel effects were measured by platelet function tests. Results Morphine neither diminished total drug exposure (AUC), which was the primary endpoint, nor significantly delayed drug absorption of prasugrel. However, morphine reduced maximal plasma concentrations (C .sub.max) of prasugrel active metabolite by 31 % (p = 0.019). Morphine slightly, but not significantly, delayed the onset of maximal inhibition of platelet plug formation under high shear rates (30 vs. 20 min). Whole blood aggregation was not influenced. Conclusions Although morphine significantly decreases the maximal plasma concentrations of prasugrel active metabolite, it does not diminish its effects on platelets to a clinically relevant degree in healthy volunteers. However, it should be considered that the observed decrease in C .sub.max of prasugrel active metabolite caused by morphine co-administration may gain relevance in STEMI patients. Clinical Trial Registration: NCT01369186, EUDRA-CT : 2010-023761-22. Author Affiliation: (1) Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria (2) Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria (3) Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria Article History: Registration Date: 15/10/2015 Received Date: 26/08/2015 Accepted Date: 15/10/2015 Online Date: 22/10/2015 Article note: T. Stimpfl and B. Jilma contributed equally.
    Keywords: Drug interactions ; Morphine ; Platelet function tests ; Prasugrel ; Vasodilator-stimulated phosphoprotein
    ISSN: 1861-0684
    E-ISSN: 1861-0692
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  • 7
    Language: English
    In: Nature Communications, 01 May 2018, Vol.9(1), pp.1-15
    Description: Cytokine-induced signaling acts as an ON/OFF switch dependent on the presence of ligands. Here the authors construct synthetic cytokine receptors responsive to synthetic ligands able to activate canonical signaling pathways.
    Keywords: Biology
    E-ISSN: 2041-1723
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  • 8
    Language: English
    In: Histochemistry and Cell Biology, 2019, Vol.151(4), pp.343-356
    Description: Histological processing of thermosensitive electrospun poly(ε-caprolactone)/poly( l -lactide) (PCL/PLA) scaffolds fails, as poly(ε-caprolactone) (PCL) is characterized by its low-melting temperature (Tm = 60 °C). Here, we present an optimized low-temperature preparation method for the histological processing of un-/cellularized thermosensitive PCL/PLA scaffolds. Our study is aimed at the establishment of an optimized dehydration and low-melting-point paraffin-embedding method of electrospun PCL/PLA scaffolds (un-/cellularized). Furthermore, we compared this method with (a) automatized dehydration and standard paraffin embedding, (b) gelatin embedding followed by automatized dehydration and standard paraffin embedding, (c) cryofixation, and (d) acrylic resin embedding methods. We investigated pepsin and proteinase K antigen retrieval for their efficiency in epitope demasking at low temperatures and evaluated protocols for immunohistochemistry and immunofluorescence for cytokeratin 7 (CK7) and in situ padlock probe technology for beta actin (ACTB). Optimized dehydration and low-melting-point paraffin embedding preserved the PCL/PLA scaffold, as the diameter and structure of its fibers were unchanged. Cells attached to the PCL/PLA scaffolds showed limited alterations in size and morphology compared to control. Epitope demasking by enzymatic pepsin digestion and immunostaining of CK7 displayed an invasion of attached cells into the scaffold. Expression of ACTB and CK7 was shown by a combination of mRNA-based in situ padlock probe technology and immunofluorescence. In contrast, gelatin stabilization followed by standard paraffin embedding led to an overall shrinkage and melting of fibers, and therefore, no further analysis was possible. Acrylic resin embedding and cyrofixation caused fiber structures that were nearly unchanged in size and diameter. However, acrylic resin-embedded scaffolds are limited to 3 µm sections, whereas cyrofixation led to a reduction of the cell size by 14% compared to low-melting paraffin embedding. The combination of low-melting-point paraffin embedding and pepsin digestion as an antigen retrieval method offers a successful opportunity for histological investigations in thermosensitive specimens.
    Keywords: PCL ; Cellularized prosthesis ; Polycaprolactone ; Polylactide acid ; Graft ; Paraffin embedding
    ISSN: 0948-6143
    E-ISSN: 1432-119X
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  • 9
    Language: English
    In: Scientific reports, 07 September 2018, Vol.8(1), pp.13430
    Description: Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function. Injury enhances calcitriol production, inducing the expression of calcitriol target genes including the antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate immune system and an important wound healing factor. We found significantly reduced hCAP18 expression in a subset of RDEB keratinocytes which could be restored by calcipotriol treatment. Reduced scratch closure in RDEB cell monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome of calcipotriol-treated cells additionally showed increased antimicrobial activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the clonogenicity and proliferation of RDEB tumor cells. The combined wound healing, anti-microbial, and anti-neoplastic effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study.
    Keywords: Wound Healing ; Anti-Bacterial Agents -- Pharmacology ; Antineoplastic Agents -- Pharmacology ; Calcitriol -- Analogs & Derivatives ; Dermatologic Agents -- Pharmacology ; Epidermolysis Bullosa -- Metabolism ; Keratinocytes -- Drug Effects
    ISSN: Scientific Reports
    E-ISSN: 2045-2322
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  • 10
    Language: English
    In: BMC Medical Informatics and Decision Making, 01 May 2009, Vol.9(1), p.25
    Description: Abstract Background Revised consensus sepsis definitions have been published in 2003. The present study was performed to compare the prevalence of different stages of sepsis and ICU mortality rates and find out the case mix within the same collective of postoperative/posttraumatic patients applying either the original 1992 ACCP/SCCM or the revised 2003 SCCM/ESICM/ACCP/ATS/SIS sepsis definitions. Methods Retrospective observational single-centre study in surgical critically ill patients admitted to an University adult ICU. From 01/2007 to 12/2007, 742 patients were surveyed daily computer-assisted with respect to different stages of sepsis. Results Within the same patient collective, applying the 2003 definitions instead of the 1992 definitions, prevalence of severe sepsis (61 vs. 56) and septic shock (205 vs. 162) was higher (p 〈 0.001). In patients with septic shock according to the 2003 definitions, mortality rate of 22% was lower than that of 27%, when the 1992 definitions were used. Risk of death was increased for those patients classified to be in septic shock with any of the definitions (OR 6.5, p = 0.001). Sensitivity to predict deaths was slightly higher with the 2003 definitions (92%) than with the 1992 definitions (88%), and specificity was lower (31% vs. 49%). Conclusion The prevalence and mortality rates of various sepsis severity stages differ if defined by the 1992 or the 2003 definitions. Thus, transferring conclusions drawn from data sets regarding severity of sepsis generated with the 1992 definitions to the same population applying the 2003 definitions may be misleading. The 1992 definitions may under-classify patients with severe sepsis.
    Keywords: Medicine
    ISSN: 1472-6947
    E-ISSN: 1472-6947
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