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排序方式: 共有946条查询结果,搜索用时 10 毫秒
81.
Beyerle A Braun A Banerjee A Ercal N Eickelberg O Kissel TH Stoeger T 《Biomaterials》2011,32(33):8694-8701
Polymeric non-viral vector systems for pulmonary application of siRNA are promising carriers, but have failed to enter clinical trials because of safety and efficiency problems. Therefore, improving their transfection efficiency, as well as their toxicological profile, is the subject of intensive research efforts. Six different poly(ethylene imine) (PEI)-based nanocarriers, with hydrophilic and hydrophobic PEG modifications, were toxicologically evaluated for pulmonary application in mice. Nanocarriers were intratracheally instilled to determine their toxicological profile, with particular focus on the inflammatory response in the lungs. Nanocarriers from both groups caused an acute inflammatory response in the lungs, albeit with different resolution kinetics and cytotoxicity. Hydrophobic modifications caused a severe inflammatory response with increased epithelial barrier permeability, accompanied by an acute antioxidant response. Hydrophilic modifications, with high PEG-grafting degrees, induced less proinflammatory effects without depleting macrophages and disrupting the epithelial/endothelial barrier in the lungs, while showing only a minor oxidative stress response. For pulmonary applications, local proinflammatory effects should be optimized by further development of nanocarriers with highly grafted PEG-PEI-based carriers or Jeffamine-modified hydrophobic PEI modifications. 相似文献
82.
Merkel OM Urbanics R Bedocs P Rozsnyay Z Rosivall L Toth M Kissel T Szebeni J 《Biomaterials》2011,32(21):4936-4942
Complement activation by polymeric gene and drug delivery systems has been overlooked in the past. As more reports appear in the literature concerning immunogenicity of polymers and their impact on gene expression patterns, it is important to address possible immune side effects of polymers, namely complement activation. Therefore, in this study the activity of low and high molecular weight poly(ethylene imine) and two PEGylated derivatives to induce complement activation were investigated in human serum. These in vitro results revealed that PEI 25 kDa caused significant and concentration dependent complement activation, whereas none of the other polymers induced such effects at their IC(50) concentrations determined by MTT-assays. To verify these in vitro results, additionally, studies were carried out in a swine model after intravenous administration, showing complement activation-related pseudoallergy (CARPA), reflected in symptoms of transient cardiopulmonary distress. Injections of PEI 25 kDa or PEI(25k)-PEG(2k)(10) at a dose of 0.05 and 0.1 mg/kg caused strong reactivity, while PEI 5 kDa and with PEI(25k)-PEG(20k)(1) were also reactogenic at 0.1 mg/kg. It was found that PEI 25 kDa caused both self- and cross-tolerance, whereas the PEG-PEIs were neither self- nor cross-reactively tachyphylactic. As a result of this study, it was shown that PEGylation of polycations with PEG of 20 kDa or higher molecular weight may be favorable. However, potential safety concerns in the development of PEI-based polymeric carriers for drugs and nucleic acids and their translation from bench to bedside need to be taken into consideration for human application. 相似文献
83.
Zheng M Liu Y Samsonova O Endres T Merkel O Kissel T 《International journal of pharmaceutics》2012,427(1):80-87
Novel biodegradable amphiphilic copolymers hy-PEI-g-PCL-b-PEG were prepared by grafting PCL-b-PEG chains onto hyper-branched poly(ethylene imine) as non-viral gene delivery vectors. Our investigations focused on the influence of graft densities of PCL-b-PEG chains on physico-chemical properties, DNA complexation and transfection efficiency. We found that the transfection efficiencies of these polymers increased at first towards an optimal graft density (n=3) and then decreased. The buffer-capacity-test showed almost exactly the same tendency as transfection efficiency. Cytotoxicity (MTT-assay) depended on the cooperation of PEG molecular weight and graft density of PCL-b-PEG chains. With increasing the graft density, cytotoxicity, zeta-potential, affinity with DNA, stability of the polyplexes and CMC-values were reduced strongly and regularly. Increasing the excess of polymer over DNA was shown to result in a decrease of the observed particle size to 100-200 nm. 相似文献
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85.
Peter Kissel 《The Journal of the Canadian Chiropractic Association》2009,53(4):282-289
Objective:
To present the characteristics and create awareness of symptomatic carpal bossing and discuss potential etiologies and the role of conservative management through the presentation of an athlete with traumatic onset of symptomatic carpal bossing.Clinical features:
This case report outlines the presentation and conservative management of an elite eighteen year old hockey player with symptomatic carpal bossing after a traumatic on ice collision. Carpal bossing is a bony, dorsal prominence in the quadrangular joint of the wrist that is inconsistently symptomatic.Intervention and outcome:
A conservative treatment plan consisting of education, reassurance, avoidance of aggravation, and soft tissue therapy allowed return to play in two weeks without restrictions or need for surgical consultation.Conclusion:
With inconsistent recurrence rates and surgical complications, the role of conservative management for symptomatic carpal bossing deserves further exploration. The conservative practitioner should be aware of the signs and symptoms of symptomatic carpal bossing to institute suitable treatment. 相似文献86.
Bakri Elsheikh MBBS MRCP Thomas Prior PhD Xiaoli Zhang PhD Robert Miller MD Stephen J. Kolb MD PhD Dan Moore PhD Walter Bradley DM FRCP Richard Barohn MD Wilson Bryan MD Deborah Gelinas MD Susan Iannaccone MD Robert Leshner MD Jerry R. Mendell MD Michelle Mendoza PT Barry Russman MD Stephen Smith MD Wendy King PT John T. Kissel MD 《Muscle & nerve》2009,40(4):652-656
To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower spinal muscular atrophy functional rating scale (SMAFRS) scores and were more likely to be non‐ambulatory. There was, however, no difference between the groups in quantitative muscle strength or pulmonary function testing. Functional scale may be a more discriminating outcome measure for SMA clinical trials. Muscle Nerve, 2009 相似文献
87.
88.
Carina Hohmann Jürgen M. Klotz Roland Radziwill Andreas H. Jacobs Thomas Kissel 《Pharmacy World & Science》2009,31(5):550-558
Objectives To improve patients health-related quality of life (HQL) after transient ischemic attack (TIA) or ischemic stroke; to guarantee
an effective secondary prevention; to increase the patient’s satisfaction with recommendations regarding their medication
by pharmacists. Setting Stroke Unit, neurological ward at the Klinikum Fulda, rehabilitation hospitals and community-based pharmacies in the region
of Fulda, Germany. Method Patients with TIA or ischemic stroke were included. The patients were assigned to an intervention group (IG) or a control
group (CG). The individual assignment of patients to IG or CG was based on the type of the local pharmacy to which patients
belong. Community-based pharmacies either delivered standard care (CG) or provided additional intensified pharmaceutical care
(PC; IG). Pharmacies delivering PC belong to a pre-existing “Quality Assurance Working Group” (QAWG). To evaluate the patient’s
HQL, the Short Form-36 (SF-36) was used at study entry in hospital and at 12 months. The secondary prevention was documented
at study entry in hospital and at 12 months. The patients’ satisfaction was measured by a questionnaire at the end of the
study. Main outcome measures Patients’ HQL; secondary prevention; patients’ satisfaction with recommendations of the pharmacists with regards to their
medication. Results Out of 1316 patients screened for participation in this study, 255 were recruited with 90/255 patients assigned to the IG
and 165/255 patients assigned to the CG. During the study, the HQL of the patients in the IG did not change significantly.
A significant decrease in the HQL was observed for the CG in 7/8 subscales and in both summary measures of the SF-36. After
12 months, 85.3% of the patients in the IG and 86.3% of the patients in the CG were treated with antiplatelet drugs or oral
anticoagulants in accordance to treatment guidelines. Patients in the IG were significantly more satisfied with the individualized
recommendations of the pharmacists than patients in the CG. Conclusion Our findings indicate that an intensified PC of patients after ischemic stroke by dedicated pharmacists may have a positive
impact on HQL and patients’ satisfaction. PC in this study had no impact on adherence to secondary prevention medication. 相似文献
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