Nanoparticles for targeted delivery of antioxidant enzymes to the brain after cerebral ischemia and reperfusion injury

Stroke is one of the major causes of death and disability in the United States. After cerebral ischemia and reperfusion injury, the generation of reactive oxygen species (ROS) and reactive nitrogen species may contribute to the disease process through alterations in the structure of DNA, RNA, proteins, and lipids. We generated various nanoparticles (liposomes, polybutylcyanoacrylate (PBCA), or poly(lactide-co-glycolide) (PLGA)) that contained active superoxide dismutase (SOD) enzyme (4,000 to 20,000 U/kg) in the mouse model of cerebral ischemia and reperfusion injury to determine the impact of these molecules. In addition, the nanoparticles were untagged or tagged with nonselective antibodies or antibodies directed against the N-methyl-𝒟-aspartate (NMDA) receptor 1. The nanoparticles containing SOD protected primary neurons in vitro from oxygen-glucose deprivation (OGD) and limited the extent of apoptosis. The nanoparticles showed protection against ischemia and reperfusion injury when applied after injury with a 50% to 60% reduction in infarct volume, reduced inflammatory markers, and improved behavior in vivo. The targeted nanoparticles not only showed enhanced protection but also showed localization to the CA regions of the hippocampus. Nanoparticles alone were not effective in reducing infarct volume. These studies show that targeted nanoparticles containing protective factors may be viable candidates for the treatment of stroke.     

后肢固定大鼠腓肠肌酶活性与银杏叶提取物EGB761的影响

目的:观察银杏叶提取物EGB761对后肢固定大鼠腓肠肌Na -K -ATP酶及Ca2 -ATP酶活性的影响,探讨其对失用性骨骼肌萎缩的防治作用。方法:实验于2005-04/2006-03在广州南方医院创伤骨科实验室(广东省重点实验室)完成。①实验分组:雄性SD大鼠24只,体质量200～260g,随机数字表法分为空白组、对照组、实验组,每组8只。②实验方法:制备大鼠骨骼肌失用性萎缩模型,将大鼠右后肢用可塑性石膏由足跖管型固定至膝上1cm处,膝关节固定于屈曲位100°,踝关节固定于跖屈60°,对照组给予蒸馏水3mL/d灌胃,实验组给予银杏叶提取物EGB761水溶液灌胃(灌胃剂量120mg/(kg·d),浓度14g/L)。③实验评估:4周后切取右后肢腓肠肌,去除腱膜、肌腱和神经,进行酶活性检测。结果:纳入大鼠24只,均进入结果分析。与空白组相比,对照组和实验组腓肠肌Na -K -ATP酶及Ca2 -ATP酶活性显著下降(P<0.05)。与对照组相比,实验组Na -K -ATP酶及Ca2 -ATP酶活性显著高于对照组(P<0.05)。结论:银杏叶提取物EGb761能够显著提高失用性萎缩骨骼肌Na -K -ATP酶及Ca2 -ATP酶活性,从而有效抑制骨骼肌失用性萎缩的发生。     

Reference intervals for circulating angiogenic cytokines.

BACKGROUND: The levels of angiogenic cytokines are important in the definition of baseline characteristics of cancers and to predict patient prognosis; however, the reference intervals for angiogenic cytokines have received only limited attention. Herein, we obtained reference intervals for angiogenic cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor, basic fibroblast growth factor, interleukin-6, vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2. METHODS: We measured these materials in serum, plasma and urine of 131 controls, according to the guidelines of the Clinical and Laboratory Standards Institute. We analyzed the association between angiogenic cytokine levels and other laboratory parameters and explored whether polymorphisms in angiogenic cytokine genes affect the levels of cytokines. RESULTS/CONCLUSIONS: These data allowed us to construct reference intervals for angiogenic cytokines, and we also observed that concentrations of angiogenic cytokines generally do not vary with genotype or haplotype. An exception was serum VEGF concentration; this level was marginally affected by the -1154 VEGF polymorphism.     

43例淋巴母细胞淋巴瘤患者临床特点及疗效分析

Objective To investigate the clinical features and treatment outcomes of different regimens in Chinese patients with lymphoblastic lymphoma(LBL). Methods Forty-three patients with LBL were retrospectively analysed, of which 30 were T-LBL, and 13 B-LBL. Results ①Most patients were young men with a median age of 21, and 63.0％ of the T-LBL patients had mediastinal masses. ② Treatment outcome could be assessed in 37 cases, of which the response rate (RR) was 81.1％ and complete remission (CR) rate was 67.6％. The RR and CR rates in patients treated with regimens for ALL (ALL-like group) and those treated with regimens for NHL(NHL-like group) were 94.4％ , 68.4％ and 83.3％ , 52.6％ , respectively. ③The estimated median overal survival(OS) and progression free survival (PFS) of hematopoietic stem cell transplantation (HSCT) group were significant longer than those of ALL-like group(P =0.018, P=0.025) and NHL-like group(P = 0. 016, P = 0. 011). The OS at 5 years in NHL-like group, ALL-like group and HSCT group were (14.4 ± 9.4) ％ , (20.2 ± 12.7) ％ and (79.5 ± 13.1) ％, respectively. Conclusion ①LBL is more common in young men, with less involvement of peripheral blood. Compared with B-LBL, T-LBL often has a mediastinal mass and serious cavity effusion. ② Intensive treatment regimens for ALL should be used in LBL. HSCT at CR1 can improve outcome obviously.     

1例总气管肿瘤切除术的围手术期护理

气管肿瘤大多发生于气管的黏膜上皮和腺体,儿童的气管肿瘤以良性居多,而成人多为恶性,占90%以上.气管肿瘤与肺和喉部的肿瘤相比,发病率要低得多,成人原发气管肿瘤仅占上呼吸道肿瘤的2%[1].     

胚胎单细胞固定技术的选择与改良

目的:在现有数种胚胎单细胞固定方法基础上,寻求一种稳定、理想的固定技术,并进行改良。方法:以4-细胞鼠胚(A组)和人体外受精(IVF)废弃胚胎(B组)之卵裂球为材料,分别以甲醇-冰醋酸(MA)法、吐温-盐酸(TH)改良法和MA+TH结合法进行固定,比较其各自的固定率、核形态等情况。结果:3种方法的固定率以MA法最低,且3种方法固定率差异有显著性(A组3种方法P=0.00621,B组3种方法P=0.00362);A组和B组固定后得到的核形态均与固定方法有明显相关性(P值分别为0.000和7.66×10-7);信号获得率和核信号评分与固定方法无明显关联(P值分别为0.186和0.0728)。结论:TH改良法固定后核形态不良,胞质残留率高;MA法核像直径大、质量较好,但技术要求高,难于普及;MA+TH结合法则核像较大,质量最好,技术易于掌握和推广。     

Bilateral internal carotid arteries ligation temporary impairs brain vasculaturev in young rats

Bilateral internal carotid artery ligation (BICL) rat model is one of the chronic cerebral hypoperfusion animal models used for investigating brain dysfunction related diseases. Cerebral blood flow decreases in different cerebral regions in a time-dependent manner after the BICL. However little is known about the cerebral vasculature change in the brain after the BICL. In the current study, the bilateral internal carotid arteries of the juvenile rats were permanently ligated and the change of the cerebral vasculature was studied 7, 14 and 21 days after the BICL. In the juvenile rats, 7 days after the BICL, the functional vascular area was decreased significantly in the anterior half of the cerebral cortex, but it had only little decrease in the posterior half of the cerebral cortex and hippocampus. However, at the time points of 14 and 21 days after the surgery, the functional vascular area throughout the whole cerebral cortex and hippocampus was almost similar to those in the sham control rats. In conclusion, the results from our current study showed that in the BICL hypoperfusion model in young rats, the brain functional vascular area was impaired initially in certain brain regions after the artery ligation, but likely to be quickly self-recovered late after. The results suggest that the brain vasculature in young rats has plasticity to external insult caused by cerebral hypoperfusion.     

Restriction of third-generation cephalosporin use decreases infection-related mortality

OBJECTIVE: To determine the effect of restriction of third-generation cephalosporin use on antibiotic resistance and the outcome of patients with infection. DESIGN: A prospective, before-after comparative study. SETTING: A general intensive care unit with 14 beds at a university-affiliated teaching hospital. PATIENTS: All patients admitted to the intensive care unit within 2 yrs. INTERVENTIONS: A new antibiotic treatment strategy was implemented during phase II. All patients with confirmed or suspected Gram-negative bacterial infections were treated mainly with antibiotics other than third-generation cephalosporins. MEASUREMENTS AND MAIN RESULTS: Antibiotic resistance among common Gram-negative bacilli and infection-related hospital mortality during phase I were compared with phase II. A 26.6% reduction in third-generation cephalosporin use (from 168.2 +/- 48.0 to 123.5 +/- 39.3 g/month, p =.021), accompanied by a 277.7% increase in cefepime use (from 10.3 +/- 19.2 to 38.9 +/- 31.7 g/month, p =.014) occurred in phase II compared with phase I. This was accompanied by a significant decrease in reduced susceptibility of Gram-negative bacilli to third-generation cephalosporins (p <.05), mainly because of the improved susceptibility of Escherichia coli and Klebsiella species (p <.05). Infection-related hospital mortality was significantly lower in phase II (19.3% vs. 36.3%, p =.014). Multiple logistic regression analysis demonstrated lower respiratory tract infection, the status of immunocompromise, and continuous veno-venous hemofiltration as independent risk factors for infection-related hospital mortality (p <.05), whereas infection with E. coli or Klebsiella species (p =.039) and restriction of third-generation cephalosporin use (p =.025) were associated with a significantly lower mortality rate. CONCLUSIONS: Restriction of third-generation cephalosporin use may improve the antibiotic susceptibility and reduce infection-related hospital mortality in critically ill patients.     

"可波动的误差参照标准"结果和意义—附Beckman CX9型生化分析仪函变质控稳定性与实用性论证

针对自动化仪器在稳定的函数变化率（简称函变）因素条件下，可因不同质量控制物的测定变异或随机差异而存在不同的可波动的误差，导致不同质控规则的不同质控性能特征的影响，提出选择标准物质来作为可波动的误差参照标准的简便、实用方法，既能适应临床高效检验的要求，达到一体化质控性能特征，又能为室内质控（IQC）增收节支降低各成本。