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1.
Christopher D Hue Frances S Cho Siqi Cao Cameron R ”Dale” Bass David F Meaney Barclay Morrison III 《Journal of cerebral blood flow and metabolism》2015,35(7):1191-1198
Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α+ isoform but not the α− isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury. 相似文献
2.
Hsiao-Hsuan Kuo Ran Fan Nina Dvorina Andres Chiesa-Vottero William M. Baldwin III 《Journal of the American Society of Nephrology : JASN》2015,26(4):855-863
Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses. 相似文献
3.
Feasibility and Diagnostic Potential of Pulmonary Transit Time Measurement by Contrast Echocardiography: A Pilot Study
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目的:研究Visumax飞秒激光辅助的准分子激光原位角膜磨镶术(LASIK)术中不透明气泡层(OBL)产生的类型、相关影响因素及其临床意义。方法:回顾性分析。收集2016 年7 月1 日至8 月20 日在南京医科大学附属眼科医院行飞秒LASIK的患者154 例(300 眼)的临床资料,等效球镜度为(-5.88±1.51)D。飞秒激光采用Zeiss公司 Visumax飞秒激光仪,将术中产生的OBL分为瓣外OBL、瓣内快速OBL和瓣内慢速OBL。300 眼按角膜曲率平均K值分为A组(<42 D)、B组(42~46 D)和C组(>46 D);按角膜瓣的厚度分为D组(100 μm)、E组(110 μm)和F组(120 μm);按角膜厚度分为G组(<500 μm)、H组(500~540 μm)和I组(>540 μm)。统计不同角膜曲率、角膜瓣厚度、角膜厚度情况下3 种OBL产生的比例,并采用多元Logistic回归模型进行统计分析。结果:300 眼均发生OBL。以瓣外OBL作为参照,角膜瓣越薄,越容易出现瓣内快速OBL(r=-0.719,P=0.034)和瓣内慢速OBL(r=-0.875,P=0.044)。以瓣内慢速OBL作为参照,角膜曲率越高,越容易出现瓣内快速OBL(r=0.923,P=0.046);角膜瓣越厚,越容易出现瓣外OBL(r=0.897,P=0.044)。结论:OBL的产生与角膜曲率、角膜瓣厚度、角膜厚度均存在一定的相关性,但瓣外OBL、瓣内快速OBL和瓣内慢速OBL对Visumax飞秒激光辅助的LASIK术后视觉质量的影响及远期疗效仍有待进一步观察研究。 相似文献
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目的:制备高表达GM-CSF的淋巴瘤细胞系,观察淋巴瘤细胞转染GM-CSF基因后生物学特性的改变。方法:将小鼠GF-CSF真核表达质粒用电穿孔法导入小鼠淋巴瘤细胞系RMA,有限稀释法制备单个细胞克隆,经RT-PCR,骨髓祖细胞增殖实验和集落形成实验筛选相对高表达GM-CSF的RMA克隆,并观察其生物学特性的改变。结果:获得了高表达GM-CS的RMA细胞系,其同基因动物体内致瘤性降低。结论:淋巴瘤细胞系RMA转染GM-CSF基因后致瘤性降低。 相似文献
9.
R. P. Heaney T. M. Zizic I. Fogelman W. P. Olszynski P. Geusens C. Kasibhatla N. Alsayed G. Isaia M. W. Davie C. H. Chesnut III 《Osteoporosis international》2002,13(6):501-505
Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy
in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined.
We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical
trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up
to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4%
in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval
37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were
stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of
70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women
with osteoporosis, with a similar magnitude of effect early and late after the menopause.
Received: 12 September 2001 / Accepted: 11 December 2001 相似文献
10.
Alexandros Karabetsos MD Dr ; George Karachalios MD Dr ; Paraskevoula Bourlinou RN Nurse ; Asimina Reppa RN Nurse ; Rozeta Koutri MD Dr ; Androniki Fotiadou MD Dr 《Headache》1997,37(1):12-14
The efficacy and safety of ketoprofen and paracetamol were compared for the treatment of acute migraine in a randomized, double-blind study of 64 patients. Thirty-four patients received ketoprofen 100 mg intramuscularly, and 30 patients received paracetamol 500 mg intramuscularly. Partial or complete relief of pain and other symptoms was achieved 15 to 20 minutes after administration in the ketoprofen group and within 35 minutes in the paracetamol group. Complete relief of pain was achieved within 30 to 40 minutes after ketoprofen in 28 patients (82.5%) compared to 5 patients (17.5%) in the paracetamol group. Six of the patients treated with ketoprofen needed a second dose for complete relief of pain during the 4-hour follow-up period. Side effects were rare and minimal. Our findings suggest that ketoprofen produced statistically significant benefit in the treatment of acute migraine. 相似文献