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N. Virgili P. Mancera C. Chanvillard A. Wegner B. Wappenhans M. J. Rodríguez C. Infante-Duarte J. F. Espinosa-Parrilla M. Pugliese 《Journal of neuroimmune pharmacology》2014,9(4):558-568
Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4+ T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect. 相似文献
34.
Synthesis,Polymorphism and Thermal Decomposition Process of (n-C4H9)4NRE(BH4)4 for RE = Ho,Tm and Yb
In total, three novel organic derivatives of lanthanide borohydrides, n-But4NRE(BH4)4 (TBAREB), RE = Ho, Tm, Yb, have been prepared utilizing mechanochemical synthesis and purified via solvent extraction. Studies by single crystal and powder X-ray diffraction (SC-XRD and PXRD) revealed that they crystalize in two polymorphic forms, α- and β-TBAREB, adopting monoclinic (P21/c) and orthorhombic (Pnna) unit cells, previously found in TBAYB and TBAScB, respectively. Thermal decomposition of these compounds has been investigated using thermogravimetric analysis and differential scanning calorimetry (TGA/DSC) measurements, along with the analysis of the gaseous products with mass spectrometry (MS) and with analysis of the solid decomposition products with PXRD. TBAHoB and TBAYbB melt around 75 °C, which renders them new ionic liquids with relatively low melting points among borohydrides. 相似文献
35.
Diverse HIV-1 subtypes and clinical, laboratory and behavioral factors in a recently infected US military cohort 总被引:5,自引:0,他引:5
36.
R H Gundel P Kinkade C A Torcellini C C Clarke J Watrous S Desai C A Homon P R Farina C D Wegner 《The American review of respiratory disease》1991,144(1):76-82
We examined the release of bronchoactive mediators into the airways of allergic primates during the acute response to specific antigen inhalation. Twelve adult male cynomolgus monkeys (Macaca fascicularis) with a naturally occurring respiratory sensitivity to inhaled Ascaris suum extract were anesthetized and intubated for each study. Respiratory system resistance (Rrs) and dynamic lung compliance (CLdyn) were measured before and after antigen inhalation, and the release of mediators into the airways was assessed by bronchoalveolar lavage (BAL). BAL samples were concentrated approximately 5-fold before quantitation of LTC4 and PGD2 by RP-HPLC and radioimmunoassay and histamine by a fluorometric assay. Antigen inhalation resulted in a 40-fold increase in BAL levels of i-LTC4 (1.5 +/- 0.7 to 41.6 +/- 12.7 ng, p less than 0.01), a 10-fold increase in i-PGD2 (2.4 +/- 0.9 to 25.9 +/- 5.5 ng, p less than 0.01), and a 20-fold increase in BAL histamine (1.0 +/- 1.5 to 21.4 +/- 2.3 micrograms, p less than 0.01). Dexamethasone (n = 7) inhibited the antigen-induced increase in BAL i-LTC4 (71 +/- 6%, p less than 0.01) and i-PGD2 (52 +/- 8%, p less than 0.05) while weakly inhibiting histamine release (43 +/- 10%). Indomethacin (n = 7) had a variable effect on i-LTC4 levels (6 +/- 51%), strongly inhibited i-PGD2 (88 +/- 9%, p less than 0.01), and had no effect on histamine release (25 +/- 8%). Pretreatment with iodoxamide tromethamine significantly blocked the release of each mediator, but mepyramine, an H1 antagonist, had no effect on mediator release.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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38.
Birke Schneider Anastasios Athanasiadis Johannes Schwab Wolfgang Pistner Uta Gottwald Ralph Schoeller Wolfgang Toepel Klaus-D. Winter Christoph Stellbrink Tobias Müller-Honold Christian Wegner Udo Sechtem 《International journal of cardiology》2014
Objective
This study evaluated the frequency, severity and outcome of complications in the clinical course of tako-tsubo cardiomyopathy (TTC).Background
TTC is regarded as a benign disease since left ventricular (LV) function returns to normal within a short time. However, severe complications have been reported in selected patients.Methods
From 37 hospitals, 209 patients (189 female, age 69 ± 12 years) were prospectively included in a TTC registry.Results
Complications developed in 108/209 patients (52%); 23 (11%) had > 2 complications. Complications occurred median 1 day after symptom onset, and 77% were seen within 3 days. Arrhythmias were documented in 45/209 patients (22%) including atrial fibrillation in 32 (15%) and ventricular tachycardia in 17 (8%). Of 8 patients resuscitated (4%), 6 survived. Additional complications were right ventricular involvement (24%), pulmonary edema (13%), cardiogenic shock (7%), transient intraventricular pressure gradients (5%), LV thrombi (3%) and stroke (1%). During hospitalization, 5/209 patients (2.5%) died. Patients with complications were older (70 ± 13 vs 67 ± 10 years, p = 0.012), had a higher heart rate (91 ± 26 vs 83 ± 19/min, p = 0.025), more frequently Q\ waves on the admission ECG (36% vs 21%, p = 0.019) and a lower LV ejection fraction (47 ± 15 vs 54 ± 14%, p = 0.002). Multivariate regression analysis identified Q-waves on admission (OR 2.49, 95% CI 1.23–5.05, p = 0.021) and ejection fraction ≤ 30% (OR 4.03, 95% CI 1.04–15.67, p = 0.022) as independent predictors for complications.Conclusions
TTC may be associated with severe complications in half of the patients. Since the majority of complications occur up to day 3, monitoring is advisable for this time period. 相似文献39.
Prof. Dr. K.-P. Günther T. Wegner S. Kirschner A. Hartmann 《Operative Orthopadie und Traumatologie》2014,26(2):141-155
Objective
Restore primary center of rotation and reconstruct extensive bone defects in hip revision surgery with a modular off-label implant combined with antiprotrusion cage and metal augment, thus, achieving improved hip function.Indications
Large segmental acetabular defects with nonsupportive columns (Paprosky type 3a and 3b) in cup loosening or Girdlestone situation. In case of pelvic discontinuity posterior column-plating is possible.Contraindications
Persisting hip infection and severe systemic disorders impairing achievement of secondary stability through bony integration of metal augment.Surgical technique
Posterolateral (if dorsal column plating) or other approach. Remove loose implant and granulation tissue with sufficient exposure of bleeding bone. Size acetabular defect with trial components of augment and appropriate antiprotrusio cage. Fixation of selected metal augment with screws. Fill additional acetabular defects with morsellized bone graft. Open a slot into the ischium to fix the distal flange of the cage. If necessary, bend both flanges according to patient’s anatomy. Enter the ischium with distal flange and gradual impaction of the antiprotrusio ring. Final stabilization of the ring with several screws aiming at the posterior column or the acetabular dome. Inject cement between ring and augment to stabilize the construction and avoid metal wear. Final cement fixation of a polyethylene liner or a dual-mobility cup into the antiprotrusio ring. In pelvic discontinuity with major instability osteosynthesis of the dorsal column can be performed prior to cementation.Postoperative management
Prophylaxis of periprosthetic infection, DVT and heterotopic ossification. Physical therapy with partial weight bearing (20 kp) for 6 weeks; in discontinuity initial wheel chair mobilization.Results
Since 2008, 72 off-label implantations of a combined antiprotrusio cage and a Trabecular Metal? Augment were performed. A total of 44 patients (46 operations) were investigated at 38.8 (36–51) months postoperatively. In all, 36 patients had a bone defect according to Paprosky type 3a/b and in 3/4 patients with pelvic discontinuity additional osteosynthesis was performed. The WOMAC score increased from 39.8 (8.7–75) points preoperatively to 57.9 (16.7–97.9) points at follow-up. Migration or failure of implant components was not observed. In 11?% of dislocations and 11?% periprosthetic infections surgical revision was necessary. 相似文献40.
Andreas Junker Jadwiga Wozniak David Voigt Uta Scheidt Jack Antel Christiane Wegner Wolfgang Brück Christine Stadelmann 《Brain pathology (Zurich, Switzerland)》2020,30(3):641-652
Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue damage was associated with the extent of neuroaxonal damage. We studied a large cohort of patients diagnosed with demyelinating CNS diseases and non‐demyelinating diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the meninges and the cortex. Included were patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), carcinomatous and lymphomatous meningitis and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using myelin protein immunohistochemistry, we found cortical demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each condition showed a disease‐specific histopathological pattern. Remarkably, extensive ribbon‐like subpial demyelination was only observed in MS, thus providing an important pathogenetic and diagnostic cue. Cortical oxidative injury was detected in both demyelinating and non‐demyelinating CNS disorders. Our data demonstrate that meningeal and cortical inflammation alone accompanied by oxidative stress are not sufficient to generate the extensive subpial cortical demyelination found in MS, but require other MS‐specific factors. 相似文献