氯吡格雷联合奥扎格雷钠治疗急性缺血性卒中疗效评价

研究背景抗血小板治疗已经成为缺血性卒中的常规治疗方法,目前对其作用的肯定主要源于临床应用,迄今尚无一项能够准确评价其有效性的实验室指标。有研究证实,血小板活化程度与动脉粥样硬化和缺血性卒中相关,尤其是血小板α颗粒膜糖蛋白CD62p和溶酶体膜糖蛋白CD63均为血小板活化的重要指标。本研究旨在通过观察急性缺血性卒中患者血小板膜表面CD62p和CD63表达变化,探讨以血小板活化程度反映氯吡格雷(75 mg)、奥扎格雷钠(80 mg)与阿司匹林(0.15 g)的疗效差异。方法采用流式细胞术检测急性缺血性卒中患者氯吡格雷(75 mg)联合奥扎格雷钠(80 mg,联合治疗组)及阿司匹林单药(阿司匹林组)治疗前后血小板CD62p和CD63阳性表达率,美国国立卫生研究院卒中量表(NIHSS)评价神经功能改善程度。结果与正常对照组相比,治疗前急性缺血性卒中组患者血小板CD62p和CD63阳性表达率升高(P=0.001,0.032);治疗后CD62p和CD63阳性表达率、NIHSS评分逐步下降(均P=0.000)。与治疗前相比,治疗后联合治疗组和阿司匹林组患者血小板CD62p和CD63阳性表达率、NIHSS评分逐步下降(均P=0.000),但组间差异无统计学意义(均P>0.05)。CD62p和CD63阳性表达率在不同观察时间点与治疗分组之间不存在交互作用(F=1.403,P=0.250;F=2.830,P=0.063),但NIHSS评分在不同观察时间点与治疗分组之间存在交互作用(F=4.518,P=0.013)。结论抗血小板药物治疗急性缺血性卒中有效,但氯吡格雷与奥扎格雷钠联合治疗之疗效与阿司匹林单药治疗并无差异。缺血性卒中急性期测定血小板CD62p阳性表达率可以用于评价抗血小板药物的疗效,但CD63表达的临床价值尚待进一步研究。     

密闭性敷料支架的制备及其性能

背景：近年来创伤敷料的研究发展较快,但很少有中药联合高分子材料制备的复合密闭敷料,且现有的创伤敷料作用较局限,不能适用于任何创伤伤口。 目的：制备适用于中药载入的密闭敷料支架,并测定其性能。 方法：将壳聚糖、明胶、聚乙烯醇,壳聚糖、明胶、聚乙烯醇和海藻酸钠分别在一定条件下共混,预冻,冷冻干燥得到支架,考察两支架的吸水性、含水量、相对保湿性、透气性、孔隙率、支架的外形。 结果与结论：壳聚糖、明胶、聚乙烯醇所制成支架的吸水性、含水量、相对保湿性、孔隙率优于壳聚糖、明胶、聚乙烯醇和海藻酸钠所制成的支架,两组比较差异有显著性意义(P < 0.05)。说明壳聚糖、明胶、聚乙烯醇适宜作为密闭敷料支架材料。 关键词：敷料支架;壳聚糖;明胶;海藻酸钠;聚乙烯醇 doi:10.3969/j.issn.1673-8225.2010.29.002     

Quantification of active ingredients in suppositories by FT‐Raman spectroscopy

An efficient method for the quantitative determination of acetaminophen (AAP) and diclofenac sodium (DS) in commercial suppositories based on partial least squares (PLS) treatment of FT‐Raman spectra is described. The relative standard errors of prediction (RSEP) were calculated for calibration and validation data sets to evaluate the quality of the constructed models. In the case of DS determination, RSEP error values of 1.9 % and 2.3 % for the calibration and validation data sets, respectively, were found. For AAP these errors amounted to 1.6–2.3 % and 1.8–2.8 %, respectively, for the different calibration models. Four commercial preparations containing 5, 12.5, 16.7 and 33.3 % (w/w) AAP and one containing 5 % (w/w) DS were successfully quantified using the developed models. Concentrations derived from the developed models correlated strongly with the declared values and yielded recoveries of 99.4–100.2 % and 99.6 % for AAP and DS, respectively. The proposed procedure can be used as a fast, economic and reliable method for quantification of the active pharmaceutical ingredients in suppositories. Copyright © 2012 John Wiley & Sons, Ltd.     

Effect of sodium and acetate ions on 8-hydroxyguanine formation in irradiated aqueous solutions of DNA and 2′-deoxyguanosine 5′-monophosphate

Abstract

Purpose: The aim of this work was to study the combined effect of sodium and acetate ions on the radiation yield of 8-hydroxyguanine (8-OHG), one of the major DNA base lesions induced by free radicals.

Materials and methods: Aqueous solutions of DNA and 2′-deoxyguanosine 5′-monophosphate (dGMP) with various concentrations of sodium acetate and sodium perchlorate were γ-irradiated, enzymatically digested and analyzed by high-performance liquid chromatography (HPLC) methods.

Results: It was found that both salts decrease the 8-OHG radiation yield in the concentration range studied for both DNA and dGMP, except in the case of dGMP wherein an increase in yield occurs in the concentration range from 0.1–1 mM. The dependence of the 8-hydroxy-2′-deoxyguanosine radiation yield on the concentration of both sodium acetate and sodium perchlorate have different shapes and have steeper slopes for the DNA compared with the dGMP solutions.

Conclusions: The observed decrease in the radiation yield of 8-OHG with increasing concentrations of sodium acetate is consistent with the hypothesis that sodium acetate produces two concentration-dependent effects in the DNA solutions: (1) A conformational change in the DNA caused by Na⁺ counterions; and (2) free radical reactions related to the radiolysis of acetate ion.     

Prevention of Topical Surfactant–Induced Itch-Related Responses by Chlorogenic Acid Through the Inhibition of Increased Histamine Production in the Epidermis

Effects of chlorogenic acid on surfactant-induced itching were studied in mice. Topical application of sodium laurate increased hind-paw scratching, an itch-related response, 2 h after application, which was inhibited by topical post-treatment with chlorogenic acid. Sodium laurate increased the histamine content and 53-kDa l-histidine decarboxylase in the epidermis, which were also inhibited by post-treatment with chlorogenic acid. These results suggest that topical chlorogenic acid is effective in the prevention of itching induced by anionic surfactants. The inhibitory activity of chlorogenic acid may be due to the inhibition of an increase in histamine in the epidermis.     

Evaluation of microtransplantation of rat brain neurolemma into Xenopus laevis oocytes as a technique to study the effect of neurotoxicants on endogenous voltage-sensitive ion channels

Microtransplantation of mammalian brain neurolemma into the plasma membrane of Xenopus oocytes is used to study ion channels in their native form as they appear in the central nervous system. Use of microtransplanted neurolemma is advantageous for various reasons: tissue can be obtained from various sources and at different developmental stages; ion channels and receptors are present in their native configuration in their proper lipid environment along with appropriate auxiliary subunits; allowing the evaluation of numerous channelpathies caused by neurotoxicants in an ex vivo state. Here we show that Xenopus oocytes injected with post-natal day 90 (PND90) rat brain neurolemma fragments successfully express functional ion channels. Using a high throughput two electrode voltage clamp (TEVC) electrophysiological system, currents that were sensitive to tetrodotoxin, ω-conotoxin MVIIC, and tetraethylammonium were detected, indicating the presence of multiple voltage-sensitive ion channels (voltage-sensitive sodium (VSSC), calcium and potassium channels, respectively). The protein expression pattern for nine different VSSC isoforms (Na_v1.1–Na_v1.9) was determined in neurolemma using automated western blotting, with the predominant isoforms expressed being Na_v1.2 and Na_v1.6. VSSC were also successfully detected in the plasma membrane of Xenopus oocytes microtransplanted with neurolemma. Using this approach, a “proof-of-principle” experiment was conducted where a well-established structure-activity relationship between the neurotoxicant, 1,1,1-trichloro-2,2-di(4-chlorophenyl)ethane (DDT) and its non-neurotoxic metabolite, 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (DDE) was examined. A differential sensitivity of DDT and DDE on neurolemma-injected oocytes was determined where DDT elicited a concentration-dependent increase in TTX-sensitive inward sodium current upon pulse-depolarization whereas DDE resulted in no significant effect. Additionally, DDT resulted in a slowing of sodium channel inactivation kinetics whereas DDE was without effect. These results are consistent with the findings obtained using heterologous expression of single isoforms of rat brain VSSCs in Xenopus oocytes and with many other electrophysiological approaches, validating the use of the microtransplantation procedure as a toxicologically-relevant ex vivo assay. Once fully characterized, it is likely that this approach could be expanded to study the role of environmental toxicants and contaminants on various target tissues (e.g. neural, reproductive, developmental) from many species.     

The effect of hyperpolarizing inputs on the dynamics of a bursting pacemaker neuron model in the pre-Bötzinger complex

The pre-Bötzinger complex (pre-BötC), a subregion of the ventrolateral medulla involved in respiratory rhythm generation, contains intrinsically bursting pacemaker neurons. A previous study proposed Hodgkin–Huxley type minimal models for pacemaker neurons and predicted the effect of a hyperpolarizing input on the dynamics of a model under certain conditions. In this model, bursting is explained by the dynamics of a persistent sodium current. In the present study, the effect of a hyperpolarizing input on the dynamics of a model was investigated under variable conditions. It was observed that immediately after an input of sufficient intensity and duration, an increase in the maximal value of the gating variable h of a persistent sodium current was brought about by a decrease in the timing of the hyperpolarizing input. This corresponds to an observation that immediately after the input, a monotonic increase in the number of spikes in the neuron model was brought about by a decrease in the timing of the hyperpolarizing input. In addition, the dependency of burst duration immediately after the input on the timing of the hyperpolarizing input varied depending on the condition of input. The present study is the first to elucidate that the influence of hyperpolarizing inputs on the number of spikes within a burst in a pacemaker neuron model in the pre-BötC is dependent on the timing of the hyperpolarizing input and to clarify the possible mechanism of this influence, thereby facilitating a detailed understanding of the dynamics of a pacemaker neuron model in the pre-BötC.     

Effects of fluoride tablets on caries and fluorosis occurrence among 6‐ to 9‐year olds using fluoridated salt

Meyer‐Lueckel H, Grundmann E, Stang A. Effects of fluoride tablets on caries and fluorosis occurrence among 6‐ to 9‐year olds using fluoridated salt. Community Dent Oral Epidemiol 2010; 38: 315–323. © 2010 John Wiley & Sons A/S Abstract – Objective: The aim of this retrospective cohort study was to investigate the association between the use of fluoride tablets among users of fluoridated salt and the occurrence of caries and fluorosis. Materials and methods: We examined 583 school children aged 6–9 years in Berlin, Germany for caries‐status (modified defs ≥ 1; d₃‐level) and fluorosis occurrence on central incisors (TSIF ≥ 1). Parents completed questionnaires about several sociodemographic and oral health related factors of the previous years. To adjust for confounding, we used log‐risk regression and estimated relative risks (RR) and 95% confidence intervals. Results: The mean modified defs was 3.2 (SD = 5.9) and 58% children were caries‐free. Twenty‐two per cent of the children revealed mild fluorosis (TSIF 1 and 2). Length of fluoride tablet use was inversely associated (adjusted for age and SES) with caries‐status: 2–4 years: RR = 0.8, 95%CI: 0.7–1.0, ≥5 years: RR = 0.5, 95%CI 0.3–0.7 (reference: 0–1 year use). This inverse association could mainly be observed in children who consumed fluoridated salt as well. Relative risks for mild fluorosis were 1.8 (95%CI: 1.1–2.9) and 2.7 (95%CI: 1.6–4.5) for fluoride tablet use of 2–4 years and ≥5 years, respectively compared with 0–1 year use. Conclusions: Fluoride tablets seem to be effective in reducing the occurrence of caries in children with low caries levels in particular among those using fluoridated salt as well. However, fluoride tablets increase the occurrence of mild fluorosis in permanent incisors.