选择性头部降温对胎羊缺血性脑损伤纹状体神经元凋亡和星形胶质细胞增殖的影响

目的研究选择性头部降温对缺血性脑损伤胎羊纹状体神经元凋亡和星形胶质细胞增殖的影响。方法胎羊于妊娠117~124d时通过双侧颈动脉阻塞30min造成双侧脑缺血损伤,损伤后将胎羊随机分为:损伤组(n=10)、2h低温组(损伤后2h开始亚低温治疗,n=7)和6h低温组(损伤后6h开始亚低温治疗,n=8),另设正常对照组(n=5)。通过冷循环水进行选择性头部降温,取脑组织用免疫组化法检测胎羊纹状体caspase-3(半胱天冬氨酸酶-3),GFAP(胶质纤维酸性蛋白)和PCNA(增殖细胞核抗原)的表达。结果①纹状体神经元凋亡:正常对照组中,caspase-3表达极少(11.00±13.77),损伤组caspase-3免疫阳性细胞为177.70±48.69,明显增加(P=0.000),损伤后2h治疗组(54.14±39.44,P=0.000)和损伤后6h治疗组(122.43±52.36,P=0.017)均能减少caspase-3免疫阳性细胞。②纹状体星形胶质细胞增殖:与正常对照组(163.40±21.98)相比,缺血性脑损伤组的GFAP免疫阳性细胞明显增多(433.25±66.69,P=0.000),损伤后2h开始亚低温治疗(219.50±35.31,P=0.000)和损伤后6h开始亚低温治疗(272.50±86.20,P=0.000)均能减少GFAP免疫阳性细胞。③纹状体PCNA阳性细胞的表达:在正常对照组中,PCNA免疫阳性细胞较少,为153.40±12.46,缺血性脑损伤组的PCNA免疫阳性细胞明显增多(353.70±45.60,P=0.000),损伤后2h开始亚低温治疗(187.14±26.26,P=0.000)和损伤后6h开始亚低温治疗(230.25±67.46,P=0.000)均能减少PCNA免疫阳性细胞。结论亚低温可以抑制纹状体神经元的凋亡和星形胶质细胞的增殖,该作用可能为选择性头部降温的脑保护作用机制之一。     

Minactivin expression in human monocyte and macrophage populations

Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.     

Current thinking on chronic renal allograft rejection: issues, concerns, and recommendations from a 1997 roundtable discussion

Chronic rejection accounts for most renal allograft losses after the first year posttransplantation. On March 24 and 25, 1997, a roundtable of five transplant surgeons, two nephrologists, and one pathologist assembled in Dallas, Texas, to review critical issues surrounding chronic renal allograft rejection. This article summarizes the presentations and relevant discussions of this meeting regarding the cause of chronic rejection, clinical diagnoses, risk factors, future prospects for intervention strategies, and general recommendations for the transplant community. Growing evidence indicates that chronic rejection is the aggregate sum of irreversible immunologic and nonimmunologic injuries to the renal graft over time. A history of acute rejection episodes and inadequate immunosuppression, likely attributable to inconsistent cyclosporine exposure or poor patient compliance, are among the most recognizable immunologic risk factors for chronic rejection. Donor organ quality, delayed graft function, and other donor and recipient variables leading to reduced nephron mass are nonimmunologic factors that contribute to the progressive deterioration of renal graft function. Clinical management of renal transplant recipients should incorporate both immunologic- and nonimmunologic-based intervention strategies aimed at minimizing risk factors to thwart the progression of chronic rejection and improve long-term allograft and patient survival.     

Fear of movement/(re)injury and activity avoidance in persons with neurogenic versus vascular claudication

Background contextActivity avoidance and fear of movement/(re)injury are increasingly being recognized as important factors in the rehabilitation of persons suffering from chronic low back pain, yet these factors have not been thoroughly explored in persons suffering from neurogenic claudication resulting from lumbar spinal stenosis.PurposeTo determine, compare, and explain differences in the degree of fear of movement/(re)injury and activity avoidance in persons with neurogenic claudication, vascular claudication, and asymptomatic volunteers.Study designProspective controlled cohort study at an academic medical center.Patient sampleEighty-two adults aged between 55 and 90 years with neurogenic claudication, vascular claudication, or no back and leg symptoms.MethodsSubjects completed a visual analog scale for pain, the Center for Epidemiological Studies Depression Scale, the Quebec Back Pain Disability Scale, Short Form 36 (SF-36), and the 13-item version of the Tampa Scale for Kinesiophobia (Tampa). They were also asked to estimate their maximum walking distance.Outcome measuresThe difference in the level of fear of movement/(re)injury and activity avoidance in the two symptomatic populations, as well as the predictive validity of self-reported measures such as pain level, functional impairment, and depression in determining fear avoidance.ResultsThe total Tampa score was significantly higher in individuals with neurogenic claudication (M=31.68; standard deviation [SD]=7.56; N=39) than vascular claudication (M=24.07; SD=6.57; N=15) (p=.002), whereas both symptomatic groups were significantly different from controls (M=18.71; SD=6.3; N=28) (p<.001 vs. neurogenic; p<.05 vs. vascular). Tampa scores were strongly correlated to the Center for Epidemiological Studies Depression Scale score (r=0.515; p<.001), SF-36 Physical Functioning score (r=?0.632; p<.001), and the visual analog scale average level of pain in a week (r=0.461; p<.001). Using a standard multiple regression model (R²=0.406; F(3,62)=13.47; p<.001), the amount of functional impairment, that is, the SF-36 Physical Functioning score, was the strongest contributor to the variance in the Tampa total score (β=?0.371; p=.014). The average level of pain did not make a significant or unique contribution in predicting the Tampa total score. Functional impairment as measured by the SF-36 Physical Functioning was strongly correlated with both pain (r=?0.740; p<.001) and depression (r=?0.488; p<.001).ConclusionsPersons with neurogenic claudication have important elevations in fear and avoidance, higher than those with claudication from another source (vascular insufficiency). The impact of fear and avoidance along with other factors such as depression on pain, disability, and quality of life for persons with claudication and spinal stenosis need to be explored.