筋脉通对糖尿病大鼠坐骨神经NADPH 氧化酶p22-phox亚基表达的影响

目的观察中药筋脉通对糖尿病大鼠坐骨神经NADPH氧化酶p22-phox亚基表达的影响。方法将STZ诱导的糖尿病大鼠随机分为模型组,维生素C组,筋脉通小、中、大剂量组,并设立正常对照组,连续灌胃16周。检测各组治疗前及治疗后4、8、12、16周的体重、血糖;测定第16周时大鼠机械痛阈值;采用免疫组化法测定大鼠坐骨神经NADPH氧化酶p22-phox亚基的表达,并进行半定量分析。结果与正常组相比,各组糖尿病大鼠体重均显著下降（P〈0．01）,血糖均明显升高（P〈0．01）;与模型组比较,各治疗组大鼠体重及血糖在各时间点均无显著差异（P〉0．05）。与正常组相比,模型组、Vc组、筋脉通小、大剂量组机械痛阈值显著降低（P〈0．01）;各治疗组机械痛阈值较模型组均明最升高（P〈0．01）;与VC组比较,筋脉通中剂量组机械痛阈值显著升高（P〈0．01）。与正常组相比,模型组及各治疗组p22亚基的IOD值明显升高（P〈0．05,P〈0．01）;各治疗组p22哑基的IOD值较模型组均显著降低（P〈0．01）;与VC组比较,筋脉通中、大剂量组p22亚基IOD值显著降低（P〈0．01,P〈0．05）。结论筋脉通能显著降低大鼠坐骨神经NADPH氧化酶p22-phox亚基的表达。     

肥胖症病人血浆nesfatin-1水平变化及与BMI关系

目的探讨肥胖症病人血浆nesfatin-1水平的改变及其与体质量指数(BMI)的关系。方法检测并比较64例肥胖病人(肥胖组)及58例正常人(正常对照组)BMI和空腹血浆nesfatin-1水平。结果肥胖组病人血浆nesfatin-1水平明显低于正常对照组(t=2.52,P<0.05),血浆nesfain-1水平与BMI呈负相关(r=-0.27,P<0.05)。结论 nesfatin-1可能参与了肥胖症的发生发展。     

Cost-sharing strategies combining targeted public subsidies with private-sector delivery achieve high bednet coverage and reduced malaria transmission in Kilombero Valley, southern Tanzania

Background

Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs) for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission.

Methods

Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights) were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage.

Results

Mean net usage of 75% (11,982/16,086) across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [×4]), while the average resident (244 [×6]), users of typical nets (210 [×7]) and users of insecticidal nets (105 [×14]) enjoyed increasing benefits.

Conclusion

Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage.     

Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors

Background and purpose:

D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above.

Experimental approach:

Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure-metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography.

Key results:

Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor α (40%), interleukin-1 β (46%), CXCL1 (33%), prostaglandin E₂ (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor α and interleukin-1 β) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A₁ receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A₁ receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP.

Conclusions and implications:

In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A₁ receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain.     

Expression of Bcl-2 and Ki-67 in tamoxifen-associated endometrial polyps: comparison with postmenopausal polyps

BACKGROUND: The aim of this study was to evaluate the expression of Bcl-2 and Ki-67 in tamoxifen (TAM)-associated endometrial polyps and postmenopausal polyps. MATERIAL AND METHODS: For this purpose, a retrospective analysis of paraffin-embedded specimens was carried out. Polyps of 20 postmenopausal and 14 TAM-treated patients, 11 simple endometrial hyperplasia, 10 atypical complex endometrial hyperplasia and 8 endometrial adenocarcinoma specimens were included in the study. Hematoxylin/eosin-stained sections were evaluated. Immunohistochemical staining was performed to investigate the expression of Bcl-2 protein and the Ki-67 proliferation index. RESULTS: There was no statistically significant difference between the 5 groups with regard to Bcl- 2 staining (p > 0.05). However, Bcl-2 expression in TAM-associated polyps was higher (86%) than in the postmenopausal control group (80%). Positive Ki-67 was highest in the endometrial adenocarcinoma specimens, followed by the atypical complex endometrial hyperplasia group (p < 0.0001). Compared to these 2 groups, Ki- 67 expression was lower in TAM-associated polyps, but Ki-67 indexes were significantly higher in the TAM-associated group than in the control group (p < 0.0001). CONCLUSION: Since TAM-associated polyps tend to have higher proliferation indexes and Ki-67 ratios than control groups, we suggest that they are likely to have a higher malignant potential.     

法氏囊活性肽-Ⅱ对肿瘤细胞增殖的抑制作用及其可能机制

目的： 研究法氏囊活性肽（Bursal-derived pentapeptide,BPP）-Ⅱ对肿瘤细胞增殖的抑制作用及其可能的作用机制。 方法： 采用不同质量浓度(0.02、0.2、2、20 μg/ml)的BPP-Ⅱ分别处理小鼠B细胞淋巴瘤细胞WEHI-231、人鼻咽癌细胞CNE、大鼠肝癌细胞RH-35和正常细胞系人胚肾细胞293、猪肾细胞PK15、中国仓鼠卵巢细胞CHO,48 h后采用MTT法检测细胞增殖情况;以双荧光素酶报告系统和Western blotting方法检测BPP-Ⅱ对荧光素酶标记的p53-Luc质粒转染的Vero细胞中 p53 转录活性和P53蛋白表达的影响;利用噬菌体随机12肽库筛选BPP-Ⅱ特异性结合肽,人工合成BPP-Ⅱ结合肽,采用MTT法检测BPP-Ⅱ结合肽对BPP-Ⅱ抗WEHI-231细胞增殖能力的影响。 结果： 2和20 μg/ml 的BPP-Ⅱ对肿瘤细胞WEHI-231 、CNE、RH-35的增殖均有抑制作用（均P<0.05）,而对正常细胞系293、PK15、CHO的增殖均不表现出抑制作用。BPP-Ⅱ明显激活 p53 基因的转录,并上调P53蛋白的表达。应用噬菌体展示技术筛选获得3个BPP-Ⅱ结合肽P3-12、P5-12、P6-12,其中2和20 μg/ml的P3-12能显著抑制BPP-Ⅱ的抗WEHI-231细胞增殖能力\[（97.5±3.4）%、（98.9±3.5）% vs （86.3±1.9）%, P<0.05 \];20 μg/ml 的P5-12和P6-12均能显著抑制BPP-Ⅱ的抗WEHI-231细胞增殖能力\[（96.7±3.1）%、（95.4±3.8）% vs （86.3±1.9）%,P<0.05\]。 结论： BPP-Ⅱ可特异性抑制WEHI-231、CNE、RH-35等肿瘤细胞增殖,其机制可能与激动 p53 信号通路有关。