Interaction of a Neutral Endopeptidase Inhibitor with an ANP-C Receptor Ligand in Anesthetized Dogs

Inhibition of important degradative pathways of atrial natriuretic peptide (ANP) in vivo could be a valuable therapeutic tool for regulating endogenous levels of ANP. The aim was to investigate the in vivo effects of both blockade of atrial natriuretic peptide clearance receptor and inhibition of neutral endopeptidase 24.11, an enzyme shown to be involved in ANP breakdown. Therefore, we infused a specific neutral endopeptidase inhibitor ((S)-thiorphan) and an ANP-C receptor ligand (AP 811) alone or in combination into anaesthetized beagle dogs.

Compared with vehicle controls, coadministration of (S)-thiorphan and AP 811 (100μg/kg/min and 10μg/kg/min, resp.) had greater effects on endocrine and renal parameters than administration of either substance alone.     

Amelioration effect of bovine casein glycomacropeptide on ulcerative colitis in mice

To explore the mechanism for amelioration effect of bovine casein glycomacropeptide on oxazolone-induced ulcerative colitis in mice. BALB/c mice were divided into four groups as follows: (1) healthy control, (2) ulcerative colitis model control, (3) casein glycomacropeptide-supplemented ulcerative colitis model (CGMP group), and (4) sulfasalazine-supplemented ulcerative colitis model (SASP group). At the end of the administration period, serum IL-1β, IL-2, IL-4, IL-5, IFN-γ, TNF-α, and IL-10 were measured by cytometric bead array and enzyme-linked immunosorbent assay, and mitogen-activated protein kinase p38 and NF-κB p65 were determined by Western blotting. The results demonstrated the inactivation of NF-κB and MAPK signaling pathways and the downregulation of the serum levels of IL-1β, IL-5, IFN-γ, and TNF-α and upregulation of IL-10 production. These changes may be associated with amelioration of oxazolone-induced ulcerative colitis by bovine casein glycomacropeptide.     

不同海拔地区人群环核苷酸的改变

本文以放射免疫法研究了不同海拔高度人群的血浆环核苷酸变化.发现:在中度高原机体环核苷酸呈低水平调控,细胞代谢适度降低,有利于机体内环境稳定;在高原的世居藏民,可能机体已产生适应性获得性遗传因素,环核苷酸调控正常,而同一地区的移居者,环核苷酸比值下降,形成了机体的生理和病理的双向改变。     

C-type natriuretic peptide regulates sperm capacitation by the cGMP/PKG signalling pathway via Ca2+ influx and tyrosine phosphorylation

Research question

What is the effect of C-type natriuretic peptide (CNP) on human sperm capacitation in vitro and what is the mechanism of this effect?

浅谈接受美国FDA现场检查的体会

本文介绍了美国FDA现场检查的目的和检查程序,讲解了FDA现场检查的迎审对策,包括现场检查的基本原则,文件和现场准备,有效组织迎审团队,认真研究审核思路,加强GMP意识培养,历史检查问题的整改。     

栀子对急性胰腺炎时胰腺细胞膜功能的影响

本文观察了栀子对大鼠急性胰腺炎时胰腺细胞膜功能的影响。结果显示：（１）模型组胰腺细胞膜上的Ｎａ＋－Ｋ＋－ＡＴＰ酶和Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶活性均明显低于正常组（Ｐ＜０．０１），用栀子治疗可使其保持正常。（２）治疗组的ｃＡＭＰ虽无明显变化，但ｃＧＭＰ明显降低，ｃＡＭＰ／ｃＧＭＰ比值显著增加（Ｐ＜０．００１）。（３）模型组血清乳酸脱氢酶活性明显增高，而胰腺组织中的活性则降低，治疗组与正常组相近。（４）胰腺炎时血清淀粉酶活性显著增高（Ｐ＜０．０１），治疗组与正常组很接近。上述结果表明栀子对大鼠急性胰腺炎时胰腺细胞膜的功能具有保护作用。     

支气管哮喘患者血浆环核苷酸的变化及其临床意义

应用放射免疫分析法(RIA)对26例支气管哮喘患哮喘发作期和缓解期分别进行血浆环磷酸腺苷(CAMP)和环磷酸鸟苷(CGMP)含量测定，结果表明哮喘发作期血浆CAMP和CGMP均明显低于健康对照组(分别P<0．01)，缓解期CGMP恢复正常，而CAMp仍处于较低水平。提示气道炎症性变化在哮喘缓解期并未完全消失，仍有复发的可能性，应设法提高细胞内CAMP的含量可望从根本上缓解哮喘病。     

吸入NO对婴幼儿体外循环中cGMP、ICAM-1的影响及意义

目的探讨吸入一氧化氮（Nitric oxide，NO）对婴幼儿体外循环手术中环磷酸鸟苷（cGMP）、细胞间粘附分子-1（ICAM-1）的影响及意义。方法将104例患室间隔缺损的婴幼儿随机分为对照组和N0组，N0组在体外循环期间吸入40ppm NO直至关胸。在体外循环前、主动脉开放后1、3、5、10min分别取右上肺静脉血和右心房血用于cGMP、ICAM—1的测定。同时采集动脉血行血气分析，计算动脉血氧含量（CaO2）、动脉血氧饱和度（SaO2）。结果NO组cGMP、SaO2和PaO2水平较对照组增高（P〈0．01），ICAM-1则较对照组明显降低（P〈0．05）。结论NO能抑制白细胞的粘附、聚集和激活，改善肺微循环，从而减轻体外循环并发症。     

CHRONIC NITRIC OXIDE INHIBITION AGGRAVATES HYPERTENSION IN ERYTHROPOIETIN-TREATED RENAL FAILURE RATS

Alterations in nitric oxide (NO) and endothelin-1 (ET-1) production have recently been reported in erythropoietin (r-HuEPO)-induced hypertension in renal failure rats. The present study was designed to evaluate the effect of NO synthase inhibition with the L-arginine analog N^G-nitro-L-arginine methyl ester (L-NAME) on blood pressure (BP) and ET-1 production in control and in uremic rats treated or not treated with r-HuEPO. Renal failure was induced by a two-stage 5/6 nephrectomy. Control and uremic rats were studied separately and subdivided into four groups: vehicle, r-HuEPO, L-NAME + vehicle and L-NAME + r-HuEPO. L-NAME (100 mg/kg/day), r-HuEPO (100 U/kg, subcutaneously, three times per week), the vehicle or both were administered during 4 weeks in control rats and during 2 weeks in uremic rats. Systolic BP was recorded before and after the onset of treatment at weeks 2 and 4 in control rats and at weeks 1 and 2 in uremic rats. Hematocrit, serum creatinine, plasma, blood vessel (thoracic aorta and mesenteric artery bed) and renal cortex immunoreactive (ir) ET-1 concentrations were measured at the end of the protocol. L-NAME enhanced BP in control and uremic rats and the increase was significantly higher in uremic rats under r-HuEPO therapy (222 ± 7 mmHg vs 198 ± 6 mmHg, p<0.05). L-NAME induced an increase in thoracic aorta ir-ET-1 concentrations in control and uremic rats. In contrast, ir-ET-1 concentrations were unchanged in the mesenteric arterial bed and the renal cortex of control and uremic animals. R-HuEPO increased thoracic aorta ir-ET-1 contents in L-NAME treated control and uremic rats. These results underline the important role of NO release in opposing the action of vasopressors on blood vessel tone which appears more important in uremic rats treated with r-HuEPO. L-NAME treatment increased large vessel, but not small resistance artery ir-ET-1 concentrations, suggesting differential regulation of ET-1 production in different vascular beds under chronic NO synthase inhibition.     

FDA医药产品CGMP相关警告信分析

目的:为我国企业把握世界医药产品质量管理的趋势和改进质量管理水平提供参考。方法:对2002~2006年间美国食品与药品管理局(FDA)发布的医药产品现行药品生产质量管理规范相关的警告信进行统计分析,探讨FDA对医药产品质量管理体系的监管重点和意图。结果与结论:FDA警告信的内容非常有价值,对把握世界医药产品质量管理的趋势和改进质量管理水平有很大帮助。我国企业可以从FDA对医药产品的监管重点、意图和现场检查等方面来整理思路,发现企业在质量管理体系方面存在的问题和进行改进的方法。