Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells

The effect of the KCNQ channel blockers XE991, chromanol 293B and linopirdine, was studied on voltage-dependent K+ currents in smooth muscle cells dissociated freshly from mouse portal vein (mPV) and isometric tension recordings from whole mPV. Voltage clamp experiments showed XE991 inhibited an outward current in a concentration-dependent manner with an IC50 of 5.8 microM. Block was voltage independent. Chromanol 293B and linopirdine also blocked the voltage-dependent K+ current but were less potent than XE991. At least two components--a linear (I(linear)) and an outward relaxation (I(out))--contributed to the XE991-sensitive conductance. XE991-sensitive currents were sustained at all test potentials and XE991 inhibited the enhanced holding current at -60 mV produced by bathing cells in an external solution containing 36 mM KCl. Current clamp experiments in the perforated-patch configuration showed XE991 and linopirdine depolarised the resting membrane potential and augmented the evoked response in a concentration-dependent manner. In functional experiments the spontaneous contractile activity of the mPV was increased significantly by XE991 and linopirdine. The stimulatory effect of XE991 was not affected by the presence of 4-AP, glibenclamide nor paxilline. These data provide evidence for an important role for KCNQ channels in governing cellular excitability in mPV smooth muscle cells.     

2型糖尿病患者血小板活化与肾病的关系

目的探索血小板活化异常与糖尿病肾病（DN）的关系。方法我们采用流式细胞术检测116例2型糖尿病（DM）患者周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆α-颗粒膜蛋白（GMP140）含量测定（ELISA法），并依据24h尿白蛋白排出率（UAER）将其分为正常白蛋白尿组（DM1）、微量白蛋白尿组（DM2）、大量白蛋白尿组（DM3），并与40例正常人对照（NC）。结果周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆GMP140在DM各组均较Nc组升高。特别是DM2，DM3组较NC组明显升高。DM合并高血压者周围血中CD62p^＋，CD63^＋，CD31^＋，CD41^＋及血浆GMP140均较无高血压者为高（P〈0．05）。结论血小板活化的增强可能与DN的发生、发展相关。     

透皮促进剂对肤康祛斑凝胶体外透皮吸收的影响

目的考察透皮促渗剂对肤康祛斑凝胶的主药熊果苷体外经皮渗透的影响。方法对优化后的肤康祛斑凝胶处方,以大鼠离体皮肤作为渗透屏障,用高效液相色谱法测定凝胶中熊果苷经皮透入接收液含量。考察氮酮、氮酮-薄荷油、氮酮-冰片作为促渗剂对熊果苷透皮吸收的影响。结果肤康祛斑凝胶中熊果苷的体外累积渗透率符合Weibull分布,以氮酮-薄荷油作为促渗剂的处方中,熊果苷累积渗透率最高,渗透促进剂的促透效果为:氮酮-薄荷油>氮酮-冰片>氮酮。结论以氮酮-薄荷油作为促渗剂,对熊果苷有较好的促渗作用。     

拓扑替康血液毒性反应的观察与研究

目的:观察拓扑替康的血液毒性反应,评价拓扑替康在临床应用的安全性。方法:113例初次接受3个周期化疗的非小细胞肺癌患者分为三组,TP组53例(拓扑替康0.75mg/m2,顺铂20mg/m2,第1～5天);NP组30例(去甲长春花碱25mg/m2,第1,8天,顺铂20mg/m2,第1～5天);HP组30例(羟基喜树碱6mg/m2,顺铂20mg/m2,第1～5天);21天为1个周期。第3周期末评价血液毒性。结果:化疗有效率TP组39.62%,NP组33.33%,HP组30.00%,组间比较无显著性差异(P>0.05);三组血液毒性反应中,TP组白细胞Ⅲ级下降18例,Ⅳ级15例,Ⅲ～Ⅳ级下降占62.26%,白细胞Ⅲ～Ⅳ级下降与NP和HP组比较均有显著性差异(P<0.05);TP组血小板Ⅲ级下降15例,Ⅳ级下降13例,Ⅲ～Ⅳ级下降占52.83%。血小板Ⅲ～Ⅳ级下降反应与NP组和HP组比较也有显著性差异(P<0.05)。结论:拓扑替康具有较重的血液毒性反应,尤其是Ⅲ～Ⅳ级反应,以白细胞和血小板下降为主。临床应用期间应注意血象监测,适时采取措施,即使发生Ⅲ～Ⅳ级骨髓抑制反应,对患者也是安全的。     

Phthalates rapidly increase production of reactive oxygen species in vivo: role of Kupffer cells

The role of oxidants in the mechanism of tumor promotion by peroxisome proliferators remains controversial. The idea that induction of acyl-coenzyme A oxidase leads to increased production of H(2)O(2), which damages DNA, seems unlikely; still, free radicals might be important in signaling in specialized cell types such as Kupffer cells, which produce mitogens. Because hard evidence for increased oxidant production in vivo after treatment with peroxisome proliferators is lacking, the spin-trapping technique and electron spin resonance spectroscopy were used. Rats were given di(2-ethylhexyl) phthalate (DEHP) acutely. The spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was also given and bile samples were collected for 4 h. Under these conditions, the intensity of the six-line radical adduct signal increased to a maximum value of 2.5-fold 2 h after administration of DEHP, before peroxisomal oxidases were induced. Furthermore, DEHP given with [(13)C(2)]dimethyl sulfoxide produced a 12-line electron spin resonance spectrum, providing evidence that DEHP stimulates (*)OH radical formation in vivo. Furthermore, when rats were pretreated with dietary glycine, which inactivates Kupffer cells, DEHP did not increase radical signals. Moreover, similar treatments were performed in knockout mice deficient in NADPH oxidase (p47(phox) subunit). Importantly, DEHP increased oxidant production in wild-type but not in NADPH oxidase-deficient mice. These data provide evidence for the hypothesis that the molecular source of free radicals induced by peroxisome proliferators is NADPH oxidase in Kupffer cells. On the contrary, radical adduct formation was not affected in peroxisome proliferator-activated receptor alpha knockout mice. These observations represent the first direct, in vivo evidence that phthalates increase free radicals in liver before peroxisomal oxidases are induced.     

薄荷醇及其受体TRPM8与肿瘤关系研究进展

薄荷是一种被广泛使用的植物药和食品添加剂,其发挥功能的主要成分为薄荷醇。研究发现薄荷醇具有抗炎镇痛、抗菌抗病毒及止咳等多种生理功能。近年来,研究发现薄荷醇具有明显的抗肿瘤活性,能抑制多种恶性肿瘤的生长和演进。然而,也有研究发现使用添加薄荷醇的香烟制品其肺癌发病率明显高于一般烟民。该文对薄荷醇的生理功能及其受体TRPM8进行综述,着重对近年来薄荷醇及其受体与肿瘤关系的研究进展进行综述,并探讨薄荷醇在临床应用的局限性和不良反应,为后续的科学研究及指导临床提供参考。     

视功能指数量表(VF-14)的修订及评价

目的:对视功能指数量表(VF-14)进行修订并对中文修订本进行信效度评价,为探索国内适宜的视功能评价工具提供依据。方法:选取眼科专家及年龄相关性白内障患者为研究对象,收集量表的修订资料形成修订本;选取年龄相关性白内障患者作为研究对象,收集其一般情况及量表资料。采用t检验、相关分析等统计方法对量表的信度效度进行分析。结果:VF-14量表中文修订本的信度:(1)重测信度:量表各条目和总分的ICC范围值在0.814～0.976;(2)内部一致性:量表的Cronbachα系数为0.916;(3)评定者间信度:量表各条目和总分的ICC范围值在0.854～0.996;(4)分半信度:量表的分半信度系数为0.817。VF-14量表中文修订本的效度:量表的条目包括了所要测量视功能的各个方面;采用术前及术后视功能生存质量量表(VRQOL)得分与VF-14中文修订本得分做相关分析,相关系数分别为0.67和0.46;采用50例患者术前术后VF-14中文修订本得分进行t检验得t=17.18,P<0.05;采用患者主观视功能改善程度与量表分值变化做相关分析,显示量表的相关系数在0.35～0.62之间。结论:视功能指数量表(VF-14)中文修订本的信度效度较好。     

增殖性糖尿病视网膜病变多次手术临床分析

目的：探讨增殖性糖尿病视网膜病变玻璃体切割术后多次手术的原因及处理。方法：回顾性分析3a来因增殖性糖尿病视网膜病变行玻璃体切割术后需要再次手术的患者。结果：患者189眼术后需要再次进行手术的为24例26眼（占总观察眼数13.8%）。分别是：玻璃体再积血3眼,前房积血1眼,视网膜脱离11眼（占总观察眼数5.8%,占再手术眼42.3%,其中3眼合并新生血管性青光眼）,白内障6眼（占总观察眼数3.2%）,单纯硅油取出5眼。189眼中有6眼发生了新生血管性青光眼（3.2%）,6眼均为玻璃体晶状体联合手术或玻璃体切割术后又摘除白内障病例。2次手术19眼,3次或以上手术7眼（其中5眼合并视网膜脱离）。结论：发生视网膜脱离是糖尿病视网膜病变玻璃体切割术后需要多次手术的主要原因;也占据需要3次或以上手术的主要部分。新生血管性青光眼的发生值得重视,出现视网膜脱离时要提高警惕,需要摘除晶状体时必须慎重。     

Correlation between intraocular pressure, central corneal thickness, stage of glaucoma, and demographic patient data: prospective analysis of biophysical parameters in tertiary glaucoma practice populations

PURPOSE: To determine the correlation of central corneal thickness (CCT) to Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT, PASCAL), and to glaucoma stage as assessed by cup-to-disc ratio (CDR). DESIGN: Prospective, cross-sectional tricenter observation study. PATIENTS AND METHODS: From three glaucoma specialty practices a sample of 406 independent eyes was included. After ultrasound pachymetry, intraocular pressure was measured using PASCAL and Goldmann applanation tonometry and cup-to-disc ration was reassessed. Demographic data were included in the multivariate analysis. RESULTS: Mean corneal thickness was 540 microm. African Americans and normal-tension glaucoma patients showed the lowest values (518 microm and 522 microm, respectively). These values were significantly thinner than the central corneal thickness of Caucasians (549 microm) and ocular hypertensives (564 microm). Intraocular pressure assessed by Goldmann applanation tonometry shows a significant correlation with central corneal thickness (r = 0.068, P < 0.001), whereas PASCAL is not significantly associated with central corneal thickness (r < 0.001, P = 0.997). Increased IOP is significantly correlated with large ocular pulse amplitudes (r = 0.13, P < 0.001), which is predominantly seen in ocular hypertensives. A significant negative correlation was detected between cup-to-disc ratio and central corneal thickness (r = 0.102, P < 0.001). CONCLUSION: Glaucoma patients with thin central corneal thickness are more likely to be found at an advanced stage of the disease and among those with normal-tension glaucoma and black African ancestry. Underestimation of intraocular pressure by Goldmann applanation tonometry could be one causative factor.     

准分子激光光学性柱镜矫治术治疗单纯性近视散光临床疗效分析

目的　评价准分子激光光学性柱镜矫治术 (photoastigm atic refractive keratectom y,PARK)治疗单纯近视性散光的疗效。方法　 7例 (9眼 )平均单纯近视性散光度为 - 2 .6 9± 1.0 4D,角膜散光 2 .5 0± 0 .72 D。实施PARK后随访 12～ 2 4个月。对术后视力、角膜表面形态及角膜散光的改变进行临床分析。结果　 9眼单纯近视性散光术后裸眼视力为 1.0 7± 0 .14,角膜散乐 1.16± 0 .0 9D。无角膜 Haze、“眩光”和上皮的并发症。结论　 PARK治疗单纯近视性散光安全、临床疗效好。