164 research outputs found
Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma
Objectives. Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-ODN) normalizes clinical and cytologic parameters in severe equine asthma. We hypothesized that CpG-ODN inhalation also reduces the misbalance of elastinolytic activity in asthmatic horses. Methods. Twenty asthmatic horses diagnosed by clinical examinations using a scoring system were included. All horses inhaled CpG-ODNs for 14 days in 2-day intervals. Matrix metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) concentrations were measured in tracheal aspirates using equine sandwich ELISAs before and 2 and 6 weeks after CpG-ODN inhalation. Results. MMP and TIMP concentrations correlated with the results of clinical scoring in all stages of equine asthma. Inhalation therapy led to significant reductions in clinical scores. MMP-2, MMP-9, and TIMP-2 concentrations were significantly reduced immediately, and all MMP and TIMP concentrations 6 weeks after therapy. Discussion. In equine asthma, overexpression of MMPs contributes to pathological tissue destruction, while TIMPs counteract MMPs with overexpression leading to fibrosis formation. The results of this study show that CpG-ODN inhalation may be an effective therapy to address a misbalance in equine asthma. Conclusions. Misbalance of elastinolytic activity seems to improve by CpG-ODN inhalation for at least 6 weeks posttherapy, which may reduce the remodeling of the extracellular matrix. Further studies should evaluate this effect in comparison to glucocorticoid inhalation therapy. Significance. CpG-ODN inhalation may be an effective therapy in the prevention of pulmonary fibrosis formation in equine asthma
Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment
Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-Îł in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4+ T lymphocytes in the respiratory tracts of the asthmatic horses were demonstrated to downregulate the mRNA expression of Tbet and IL-8. Concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 were significantly decreased directly after the treatment as well as six weeks post-treatment. This innovative therapeutic concept thus opens new perspectives in the treatment of severe equine asthma and possibly also that of human asthma
Strain-stiffening gels based on latent crosslinking
Gels are an increasingly important class of soft materials with applications ranging from regenerative medicine to commodity materials. A major drawback of gels is their relative mechanical weakness, which worsens further under strain. We report a new class of responsive gels with latent crosslinking moieties that exhibit strain-stiffening behavior. This property results from the lability of disulfides, initially isolated in a protected state, then activated to crosslink on-demand. The active thiol groups are induced to form inter-chain crosslinks when subjected to mechanical compression, resulting in a gel that strengthens under strain. Molecular shielding design elements regulate the strain-sensitivity and spontaneous crosslinking tendencies of the polymer network. These strain-responsive gels represent a rational design of new advanced materials with on-demand stiffening properties with potential applications in elastomers, adhesives, foams, films, and fibers
Immunomodulatory asthma therapy in the equine animal model: A doseâresponse study and evaluation of a longâterm effect
Introduction
Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticleâbound cytosineâphosphateâguanosine (CpGâGNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible longâterm effect.
Methods
In the prospective, randomised, doubleâblind clinical field study, 29 horses suffering from equine asthma received 10 inhalation treatments with either 187.5â”g CpGâGNP (CpG single dose [CpGsd]; nâ=â11), 375â”g CpGâGNP double dose (CpG double dose [CpGdd]; nâ=â9) (q48h for 20 days) or 1600â”g beclomethasone (nâ=â9) (q24h for 10 days). Each horse was examined three times: before the treatment (I), immediately after the 10 inhalations (II), and 8 weeks after the final inhalation (III). The three groups were compared according to clinical and laboratory parameters. The study examined the sustainability of the longâterm effect of the treatment after 8 weeks, as well as the tolerability of the formula as a double dose.
Results
The CpGsd resulted in a significant improvement in 82% of the parameters, the CpGdd in 72%. In the longâterm evaluation, the CpGsd showed a significant improvement in 100% of the parameters in comparison to the initial values, the CpGdd in 67%. On the immunological level, the bronchoalveolar lavage revealed a significant reduction of ILâ4, ILâ8, and interferonâÎł.
Conclusion
Both CpG groups displayed significant improvements in clinical and laboratory parameters, especially regarding the longâterm effect of CpGsd. Doubling the CpG dose did not result in any improvement in comparison to the original single dose. On the immunological level, an antiâinflammatory, as well as an immunomodulatory effect, apart from a Th2âdominated immune response, could be observed. This immunomodulatory inhalation treatment could indicate a new possibility for human allergic asthma therapy
A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model
Introduction: New therapeutic strategies to modulate the immune response of
human and equine allergic asthma are still under extensive investigation.
Immunomodulating agents stimulating T-regulatory cells offer new treatment
options beyond conventional symptomatic treatment or specific immunotherapy
for human and equine allergic airway diseases, with the goal of a homoeostatic
T-helper cell balance. The aim of this study was to evaluate the effects of a
nebulized gelatin nanoparticle-CpG formulation (CpG-GNP) with and without
specific allergens for the treatment of spontaneous allergic equine asthma as
a model for human asthma. Methods: Twenty equine asthma-affected horses were
treated either with CpG-GNP alone or CpG-GNP with allergens. Two specific
allergens were selected for each horse based on history and an in-vitro test.
Each horse received seven administrations of the respective nebulized
composition and was examined before treatment, immediately after and 6 weeks
after the treatment course. Results: Clinical parameters such as breathing
rate, indirect interpleural measurement, arterial blood gases, amount of
tracheal mucus and percentage of neutrophils and cytokines in tracheal washes
and serum samples were evaluated. Treatment with CpG-GNP alone as well as in
combinations with relevant allergens resulted in clinical improvement of nasal
discharge, breathing rate, amount of secretion and viscosity, neutrophil
percentage and partial oxygen pressure directly after and 6 weeks after
treatment. There were no significant differences between the two treatments in
clinical parameters or local cytokine profiles in the tracheal wash fluid
(IL-10, IFN-g, and IL-17). IL-4 concentrations decreased significantly in both
groups. Conclusion: Nonspecific CpG-GNP-based immunotherapy shows potential as
a treatment for equine and possibly also human allergic asthma
Search for R-Parity Violating Decays of Scalar Fermions at LEP
A search for pair-produced scalar fermions under the assumption that R-parity
is not conserved has been performed using data collected with the OPAL detector
at LEP. The data samples analysed correspond to an integrated luminosity of
about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An
important consequence of R-parity violation is that the lightest supersymmetric
particle is expected to be unstable. Searches of R-parity violating decays of
charged sleptons, sneutrinos and squarks have been performed under the
assumptions that the lightest supersymmetric particle decays promptly and that
only one of the R-parity violating couplings is dominant for each of the decay
modes considered. Such processes would yield final states consisting of
leptons, jets, or both with or without missing energy. No significant
single-like excess of events has been observed with respect to the Standard
Model expectations. Limits on the production cross- section of scalar fermions
in R-parity violating scenarios are obtained. Constraints on the supersymmetric
particle masses are also presented in an R-parity violating framework analogous
to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.
Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2
The hadronic structure function of the photon F_2^gamma is measured as a
function of Bjorken x and of the factorisation scale Q^2 using data taken by
the OPAL detector at LEP. Previous OPAL measurements of the x dependence of
F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of
F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted
by QCD, the data show positive scaling violations in F_2^gamma. Several
parameterisations of F_2^gamma are in agreement with the measurements whereas
the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001,
Ascona, Switzerlan
Search for the Standard Model Higgs Boson with the OPAL Detector at LEP
This paper summarises the search for the Standard Model Higgs boson in e+e-
collisions at centre-of-mass energies up to 209 GeV performed by the OPAL
Collaboration at LEP. The consistency of the data with the background
hypothesis and various Higgs boson mass hypotheses is examined. No indication
of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained
on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure
Search for Higgs Bosons in e+e- Collisions at 183 GeV
The data collected by the OPAL experiment at sqrts=183 GeV were used to
search for Higgs bosons which are predicted by the Standard Model and various
extensions, such as general models with two Higgs field doublets and the
Minimal Supersymmetric Standard Model (MSSM). The data correspond to an
integrated luminosity of approximately 54pb-1. None of the searches for neutral
and charged Higgs bosons have revealed an excess of events beyond the expected
background. This negative outcome, in combination with similar results from
searches at lower energies, leads to new limits for the Higgs boson masses and
other model parameters. In particular, the 95% confidence level lower limit for
the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons
can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA >
72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and
soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for
minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM
parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European
Physical Journal
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