白细胞介素12对抗原诱导小鼠过敏性气道反应的调节作用

目的:探讨气道内应用白细胞介素12(IL-12)对抗原诱导的过敏性气道反应的影响.方法:C57BL/6小鼠以卵白蛋白(OVA)免疫建立哮喘模型,在主动免疫及抗原激发阶段气道内应用IL-12,观察肺泡灌洗液细胞成分、肺部淋巴细胞产生细胞因子、外周血IgE水平变化.结果:(1)致敏阶段应用IL-12可明显抑制嗜酸粒细胞浸润和肺淋巴细胞分泌IL-5,降低血浆总IgE和抗原特异性IgE的水平;(2)抗原激发阶段应用IL-12,可明显抑制嗜酸粒细胞的浸润,抑制肺淋巴细胞产生IL-4、IL-5及增强其产生IFN-γ,但对抗原特异性IgE水平则无明显影响;(3)当在致敏和激发阶段均应用IL-12时,可明显抑制肺淋巴细胞产生IL-4、IL-5,增强IFN-γ的产生,抑制气道内嗜酸粒细胞的浸润以及血浆中IgE水平的升高.结论:气道内应用IL-12对抗原诱导的气道过敏性炎症有明显的调节作用,并与应用时机有关;为气道应用IL-12免疫治疗支气管哮喘提供了实验依据.     

我国药企应对跨国药企在知识产权方面的竞争分析

通过对比跨国药企的知识产权战略,分析我国药企在知识产权保护方面的差距,为我国医药企业实施知识产权战略提供思路.我国药企不仅要不断地加大研发投入,积极培养新药自主研发与创新能力,而且要制订和运用相应的知识产权战略,以此积极应对与跨国公司在国内外市场上的竞争.     

严重感染患者血清白蛋白动力学研究

目的了解感染状态下血清白蛋白的分解和分布动力学的变化,以进一步明确感染患者低白蛋白血症的发生机制。方法对照组10例,全部为男性健康志愿者;感染组10例,均为严重感染患者,APACHEⅡ评分8～22(平均13)。采用氯胺T法,用125I 标记人体白蛋白。所有受试者一次性从上臂静脉注射20μCi的125I白蛋白,分别在第0、1、2、4、8、12、24h,第2、3、4、5、6、7、9、11、13、15、18、22、25天抽血,测定γ射线量(dpm),拟合浓度时间曲线,计算标记白蛋白的半衰期(t1/2),分布容积(Vd),中央池向周边池的转运速率(K12)。结果感染组的125I标记白蛋白t1/2(d)明显短于对照组(8.2±1.4vs.12.5±1.7,P<0.01);感染组标记白蛋白从中央池向周边池的转运速率(K12)显著高于对照组[(4.4±1.9)×10-2/hvs.(2.4±0.6)×10-2/h,P<0.05];两组分布容积(Vd)则没有显著的差异(P>0.05)。结论在感染条件下,血清白蛋白从血管内到血管外的分布速率明显增加,白蛋白的分解速率也显著增加。     

丹参酮脂质体的药物渗漏和微粒聚结特性研究

考察了聚乙烯吡咯烷酮（PVP）以及冻融处理对丹参酮脂质体的药物渗漏和微粒聚结特性的影响。结果表明，丹参酮脂质体在4℃下贮存3、6．5个月后，未发现丹参酮有明显渗漏，处方中的PVP和冻融处理对丹参酮 的渗漏影响不明显；但PVP可提高丹参酮脂质体微粒的聚结活化能，并使脂质体ζ电位有所增大；脂质体混悬液在4℃下贮存3个月，不含PVP的样品粒度明显增大，并出现分层现象，而含有PVP的样品，其粒度变化甚微，混悬液均匀；而冻融处理也能使丹参酮脂质体的聚结活化能增大。     

Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo[1,5-a]quinazolines

Several 5-alkoxy-tetrazolo[1,5-a]quinazoline derivatives have been synthesized by reacting 2,4-dichloroquinazoline with various phenols or aliphatic alcohol and then with sodium azide. The structures of these compounds have been confirmed by IR, MS, ¹H-NMR, and elementary analysis. Anticonvulsant activities were evaluated using the maximal electroshock (MES) test. Most of the synthesized compounds displayed weak anticonvulsant activity at a dose of 300 mg/kg. Antidepressant activities were investigated by forced swimming test. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a]quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2 and 51.7% at 100 mg/kg dose level.     

Effect of luminal angiotensin II receptor antagonists on proximal tubule transport.

The proximal tubule can endogenously synthesize and secrete luminal angiotensin II at a concentration approximately 100- to 1000-fold higher than that in the systemic circulation. We have recently shown that this endogenously produced and luminally secreted angiotensin II regulates proximal tubule volume reabsorption, which is a reflection of sodium transport within this segment. In this study, we use in vivo microperfusion of angiotensin II receptor antagonists into the lumen of the proximal tubule to examine the role of the luminal AT1 and AT2 receptor in the regulation of volume reabsorption. Systemically administered (intravenous) AT1 and AT2 receptor antagonists, acting through basolateral angiotensin II receptors, have previously been shown to inhibit proximal tubule transport. Luminal perfusion of 10(-6) mol/L Dup 753 (AT1 antagonist) and 10(-6) mol/L PD 123319 (AT2 antagonist) decreased proximal tubule volume reabsorption from 2.94 +/- 0.18 to 1.65 +/- 0.18 and 1.64 +/- 0.19 nL/mm x min, respectively, P < .01. Luminal perfusion of 10(-4) mol/L CGP 42112A, another AT2 antagonist, similarly decreased volume reabsorption to 1.32 +/- 0.36 nL/nm x min, P < .01. The inhibition of transport with AT1 and AT2 antagonist was additive, as luminal perfusion of 10(-6) mol/L Dup 753 plus 10(-6) mol/L 123319 resulted in a decrease in volume reabsorption to 0.41 +/- 0.31 nL/mm x min, P < .001 v control, P < .05 v Dup 753, and P < .01 v PD 123319. These results show that endogenously produced angiotensin II regulates proximal tubule volume transport via both luminal AT1 and AT2 receptors.     

Influence of surfactant mixtures on intercellular lipid fluidity and skin barrier function

Background/aims: Surfactant mixtures are used in cosmetic and pharmaceutical formulas in order to establish product efficacy while maintaining mildness and skin lipids. The electron paramagnetic resonance (EPR) technique of the spin labeling method with a nitroxide spin probe is a valuable method in the study of biological membranes. The objective of this study was to define the influence of surfactant mixtures on intercellular lipid fluidity and correlate EPR spectral data with in vivo safety data. Methods: EPR experiment: EPR spectra of 5-doxyl stearic acid (5-DSA) labeled stratum corneum treated with sodium lauryl sulfate (SLS), sodium lauroyl glutamate (SLG) and their mixtures were measured and order parameters were calculated. Clinical testing: Fifteen healthy volunteers free of skin disease and with no history of atopic dermatitis were treated with SLS solutions (0.25%, 0.50%, 0.75%, 1.00%), 1.00% SLG solution and 1.00% surfactant mixture solutions: 0.75% SLS+0.25% SLG, 0.50% SLS+0.50% SLG, 0.25% SLS+0.75% SLG. One hundred μl of solution was applied using a polypropylene chamber for 24 h. Transepidermal water loss (TEWL) was measured with an evaporimeter before and after the application of surfactant solutions and each site was also visually graded according to Lee (1). Results: The order parameter (S) calculated from 1.00 %wt SLS treated stratum corneum was 0.56 ± 0.03, indicating disordering of lipid structure. On the contrary, the high S value (0.82 ± 0.02) for 1.00 %wt SLG suggests a reduced effect on the structured lipid, almost equaling the value of water. Treatment with 0.25 %wt, 0.50 %wt and 0.75 %wt SLS solutions revealed intermediate levels between 1.00 %wt SLG and SLS. The order parameters at each SLS concentration (0.25, 0.50, 0.75 and 1.00 %wt SLS) with 1.00 %wt SLG showed higher values than those of SLS only solutions. There were statistically significant differences between with and without 1.00 %wt SLG (P < 0.05). These results suggest that the addition of 1.00 %wt SLG inhibits the fluidization of intercellular lipid induced by SLS. The visual scores and TEWL values of 1.00% SLG solution were lower than those of the other test solutions (except for the vehicle control: deionized water). The 1.00% surfactant mixture solutions showed lower visual scores and TEWL values of the 1.00% SLS solution. An increase of SLG concentration decreased the visual scores and TEWL values. Order parameter S obtained from EPR spectra correlated with the clinical study. The correlation coefficient (r²) of visual score and TEWL values was 0.73 and 0.83, respectively. Conclusion: SLS disorder (fluidity) intercellular lipids at low concentrations, such as 0.25 %wt, presumably due to the SLS molecules being intercalated into the intercellular lipids. However, EPR spectral data suggest that the addition of 1.00 %wt SLG to an SLS solution (<1.00 %wt) inhibits the fluidization of intercellular lipid induced by SLS. A reasonable correlation between order parameters and human clinical data (visual scores and TEWL values) was observed (r²=0.73 and 0.83, respectively). The use of the EPR spin labeling method for predicting the fluidity of stratum corneum should give further insight into the mechanism of epidermal barrier disruption by surfactants and possibly other chemicals.