Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

人骨髓间充质干细胞向血管内皮细胞诱导分化的研究

目的:分析人骨髓间充质干细胞(hMSCs)和脐静脉内皮细胞(hUVECs)的基因表达差异,探讨体外基因转染诱导内皮分化的可行性以及作为血管组织工程种子细胞来源的应用前景。方法:分别从人骨髓和脐静脉分离间充质干细胞(hMSCs)和内皮细胞(hUVECs),扩增培养后进行流式细胞仪、免疫细胞化学,免疫荧光鉴定和超微结构观察。通过BiostarH-40S表达谱芯片分析,选择两者的差异表达基因,导入hMSCs,经RT-PCR、ELISA鉴定该基因的转染和表达,并分析hMSCs的内皮分化程度。结果:hMSCs表达内皮细胞的多种特异性mRNA,经VEGFl65基因瞬时转染后RT-PCR有明显条带,ELISA定量检测VEGF165蛋白表达为(707.9±11.3)ng/L,同时CD44表达明显下调38.80%,CD31则明显上调达56.82%,FI-1,FVⅢAg和CD34的表达也有不同程度升高。结论:hMSCs具有内皮分化潜能,体外基因转染诱导hMSCs产生功能性内皮细胞和组织工程化血管具有广阔前景。     

EAE大鼠SFO血红素氧合酶-1基因和蛋白表达的变化

目的：探讨实验性变态反应性脑脊髓炎（EAE）时,大鼠血红素氧合酶-1（HO-1）在穹隆下器（SF0）中的变化,为证明SFO是感受外周信息物质的早期位点之一提供依据。方法：分别用免疫组化和原位杂交方法,观察了完全福氏佐剂-豚鼠脊髓匀浆（CFA-GPSCH）诱导大鼠EAE1d、7d、14d、21d时SFO部位HO-1基因和蛋白表达的动态变化,并分析了与症状之间的相关性。结果：对照组大鼠脑仅有少量HO-1基因和蛋白表达;实验组大鼠诱导EAE后,伴随着大鼠EAE症状及脑组织病理损伤的出现和进行性加重,其HO-1基因和蛋白表达量逐渐增高;在诱导后1d,SFO部位即出现HO-1mRNA和蛋白表达,而其他脑区变化不明显;7d时进一步增多;14d时,H01蛋白表达至高峰。HO-1阳性细胞主要位于脉络丛、穹隆下器、血管“套袖样”病灶的周围,与EAE病变部位一致,此时大鼠EAE病情最重、体重减轻最显著、脑组织病理改变最明显;21d时脑组织HO-1基因和蛋白表达量逐渐下降,大鼠EAE症状也逐渐恢复。应用HO-1特异性抑制剂Snpp9后,大鼠EAE症状和脑组织病变明显减轻,说明脑组织HO-1的动态变化与EAE症状及脑组织损伤密切相关。结论：在EAE发病早期,SFO即已经感受到外界的氧化应激变化,SFO可能是外周免疫信息物质向中枢神经系统传递的重要而早期的通道之一;其次,应用HO-1抑制剂可能成为防治该病的有效方法之一。     

四链DNA(loopG4)螺旋结构的计算机模拟

对包含连续鸟嘌呤的寡核苷酸所形成两种反平行四链ＤＮＡ（统称ｌｏｏｐＧ４）的螺旋体部分进行了计算机模拟,给出了各种结构参数,发现ｌｏｏｐＧ４中的磷酸基团呈疏密相间的分布,导致与其抗衡的Ｋ＋亦呈疏密相间的分布。与先前做的平行四链ＤＮＡ相比较,平行Ｇ４的构象能最低,二沟Ｇ４和三沟Ｇ４次之。ｌｏｏｐＧ４中Ｇ四聚体的两种不同堆积方式以背对背的堆积能为低,为实验结果提供了理论支持。还探讨了能量优化过程中Ｇ４－ＤＮＡ的构象变化趋势,提示了金属离子的不同类型或不同浓度可能会导致Ｇ４－ＤＮＡ构象的改变     

Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies

Nitric oxide, a gaseous free radical, is poorly reactive with most biomolecules but highly reactive with other free radicals. Its ability to scavenge peroxyl and other damaging radicals may make it an important antioxidant in vivo, particular in the cardiovascular system, although this ability has been somewhat eclipsed in the literature by a focus on the toxicity of peroxynitrite, generated by reaction of O^·-₂ with NO^· (or of NO^- with O₂). On balance, experimental and theoretical data support the view that ONOO^- can lead to hydroxyl radical (OH^·) generation at pH 7.4, but it seems unlikely that OH^· contributes much to the cytotoxicity of ONOO^-. The cytotoxicity of ONOO^- may have been over-emphasized: its formation and rapid reaction with antioxidants may provide a mechanism of using NO^· to dispose of excess O^·-₂, or even of using O^·-₂ to dispose of excess NO^·, in order to maintain the correct balance between these radicals in vivo. Injection or instillation of “bolus” ONOO^- into animals has produced tissue injury, however, although more experiments generating ONOO^- at steady rates in vivo are required. The presence of 3-nitrotyrosine in tissues is still frequently taken as evidence of ONOO^- generation in vivo, but abundant evidence now exists to support the view that it is a biomarker of several “reactive nitrogen species”. Another under-addressed problem is the reliability of assays used to detect and measure 3-nitrotyrosine in tissues and body fluids: immunostaining results vary between laboratories and simple HPLC methods are susceptible to artefacts. Exposure of biological material to low pH (e.g. during acidic hydrolysis to liberate nitrotyrosine from proteins) or to H₂O₂ might cause artefactual generation of nitrotyrosine from NO^-₂ in the samples. This may be the origin of some of the very large values for tissue nitrotyrosine levels quoted in the literature. Nitrous acid causes not only tyrosine nitration but also DNA base deamination at low pH: these events are relevant to the human stomach since saliva and many foods are rich in nitrite. Several plant phenolics inhibit nitration and deamination in vitro, an effect that could conceivably contribute to their protective effects against gastric cancer development.     

Soil Properties and their Spatial Pattern in a Degraded Sandy Grassland under Post-grazing Restoration, Inner Mongolia, Northern China

In this study, we use classical and geostatistical methods to identify characteristics of some selected soil properties including soil particle size distribution, soil organic carbon, total nitrogen, pH and electrical conductivity and their spatial variation in a 5-year recovery degraded sandy grassland after two different grazing intensity disturbance: post-heavy-grazing restoration grassland (HGR) and post-moderately grazing restoration grassland (MGR), respectively, in Horqin steppe, Inner Mongolia, northern China. The objective was to examine effect of grazing intensity on spatial heterogeneity of soil properties. One hundred soil samples were taken from the soil layer 0–15 cm in depth of a grid of 10 m×10 m under each treatment. The results showed that soil fine fractions (very fine sand, 0.1–0.05 mm and silt + clay, <0.05 mm), soil organic carbon and total nitrogen concentrations were significant lower and their coefficients of variation significant higher under the HGR than under the MGR. Geostatistical analysis of soil heterogeneity revealed that soil particle size fractions, organic carbon and total nitrogen showed different degree of spatial dependence with exponential or spherical semivariograms on the scale measured under HGR and MGR. The spatial structured variance account for a large proportion of the sample variance in HGR plot ranging from 88% to 97% for soil particle fractions, organic C and total N, however, except for organic C (88.8%), the structured variance only account for 50% of the sample variance for soil particle fractions and total N in the MGR plot. The ranges of spatial autocorrelation for coarse-fine sand, very fine sand, silt + clay, organic C and total N were 13.7 m, 15.8 m, 15.2 m, 22.2 m and 21.9 m in HGR plot, respectively, and was smaller than in MGR plot with the corresponding distance of 350 m, 144.6 m, 45.7 m, 27.3 m and 30.3 m, respectively. This suggested that overgrazing resulted in an increase in soil heterogeneity. Soil organic C and total N were associated closely with soil particle fractions, and the kriging-interpolated maps showed that the spatial distribution of soil organic C and total N corresponded to the distribution patterns of soil particle fractions, indicating that high degree of spatial heterogeneity in soil properties was linked to the distribution of vegetative and bare sand patches. The results suggested that the degree of soil heterogeneity at field scale can be used as an index for indicating the extent of grassland desertification. Also, the changes in soil heterogeneity may in turn influence vegetative succession and restoration process of degraded sandy grassland ecosystem.     

The effect of tripeptide tyroserleutide (YSL) on animal models of hepatocarcinoma

This study aimed to observe the effects of tyroserleutide (tyrosyl-seryl-leucine, YSL) on the survival time of mice transplanted with the ascitic fluid-type hepatocarcinoma H22, as well as the inhibitory effect of tyroserleutide on the human hepatocarcinoma Bel-7402 that was transplanted into nude mice. At doses of 80, 20 and 5 microg/kg/d, tyroserleutide significantly prolonged the survival of mice transplanted with H22 tumor cells, producing survival rates of 89%, 39% and 49%, respectively, which were statistically significantly different from the saline group (P < 0.05). YSL, at doses of 80, 160 and 320 microg/kg/d significantly inhibited the growth of the human hepatocarcinoma Bel-7402 tumor in nude mice, producing inhibition of 40%, 64% and 59%, respectively; this inhibition was significantly greater than that by saline (P < 0.05). HE staining and electron microscopy of the pathological changes of the tumor in nude mice showed that YSL changed the structure Bel-7402 tumor cells that were transplanted into nude mice, and also induced tumor cell apoptosis and necrosis, which could be a mechanism by which YSL inhibits the tumor growth in animal models.     

Substituted indanylacetic acids as PPAR-alpha-gamma activators

A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.     

Erythroid differentiation denucleation factors (EDDFs) function as intrinsic, post-erythropoietin regulators for mammalian erythroid terminal differentiation

Regulatory factors other than erythropoietin (Epo) dependence, that control mammalian erythroid terminal differentiation, are currently uncertain. Here we report the existence of erythroid differentiation factors in erythroid cytoplasm. Purification of these factors from cultured Friend virus anaemia (FVA)-infected mouse splenic erythroblasts was carried out using isoelectrophoresis and high performance of liquid chromatography techniques. We have identified intracellular erythroid differentiation denucleation factors (EDDFs) that were able to mediate the events of post-Epo-dependent erythroblast terminal differentiation. Purified EDDF proteins bound specifically to the enhancer HS2 sequence of the globin gene activated the expression of haemoglobin in mouse erythroleukaemia and K562 erythroleukaemic cells and promoted them to differentiate into mature erythrocytes. EDDF proteins began to emerge at the pro-early erythroblast stages upon exposure to Epo in culture, and increased dramatically in early erythroblast stage. The dynamic of EDDF expression and its action on the key events of erythroblast differentiation and denucleation appeared to be closely consistent with its spatiotemporal distribution. These results suggest that EDDFs are the critical intracellular regulatory factors that may act as the successive regulators to Epo, responsible for the final stages of erythroid terminal differentiation.