HPLC-MAXPLOT UV检测法测定血清中丹那唑及其代谢产物

本文建立了同时测定人体血清中丹那唑(Ⅰ)及其主要代谢产物2-羟甲基妊娠素(Ⅱ)和其它代谢产物妊娠素(Ⅲ)的高效液相色谱法。方法用YWG C18柱并以甲醇—水(74:26)作为流动相,应用紫外最大吸收作图法(maxplot)检测技术,以UV 285,240nm分别测定Ⅰ,Ⅱ和Ⅲ。使原型药和代谢产物都达到较高检测灵敏度。同时对方法的专一性、准确性和精密度等方面进行了评价,并应用于临床监测。     

激活素A及其受体卵泡休止素在子痫前期胎盘中的表达

目的探讨激活素A的βA亚基及其Ⅰ型、ⅠB型和Ⅱ型受体,激活素A结合抑制蛋白卵泡休止素在子痫前期患者胎盘组织中的表达变化。方法采用逆转录半定量聚合酶链反应(RT-PCR)和免疫组织化学方法检测妊娠26、32周和38周18例健康和18例子痫前期胎盘组织中激活素A及其Ⅰ型、ⅠB型和Ⅱ型受体,卵泡休止素的表达,并比较两者的不同。结果激活素Aβ亚基在孕26、32周和38周子痫前期胎盘组织中表达较健康妊娠胎盘明显升高(P<0.05),Ⅰ型、ⅠB型和Ⅱ型受体在孕26、32周子痫前期胎盘组织表达高于健康胎盘(P<0.05),卵泡休止素的表达同健康妊娠胎盘相比无明显变化。结论激活素A及其受体在子痫前期胎盘表达增高,子痫前期发病越早,增高越明显,因此激活素A可作为妊娠期高血压疾病早期诊断的候选指标。     

用液相质谱法鉴定盐酸关附甲素在大鼠胆汁中Ⅰ相和Ⅱ相代谢产物(英文)

目的:研究盐酸关附甲素在大鼠胆汁中的代谢产物.方法:建立了液相质谱和串联质谱法(LC-MS)对关附甲素及其代谢产物鉴定的方法.大鼠静脉注射盐酸关附甲素后采集胆汁,通过与对照化合物的色谱保留时间、分子离子峰、碎片离子峰和紫外图谱对照从而鉴定Ⅰ相代谢物.胆汁经过葡萄糖醛酸酶或硫酸酯酶水解,鉴定其水解产物(苷元),从而确定Ⅱ相结合物,再通过LC-MS分离和确定分子离子峰,最后利用MS-MS寻找特征子离子和母离子的方法进行验证.结果:大鼠胆汁中存在Ⅰ相代谢物关附壬素;Ⅱ相结合物经葡萄糖醛酸酶和硫酸酯酶酶解后,出现关附甲素和关附壬素;LC-MS检测发现胆汁中m/z 606和 510两个准分子离子峰,推测分别为关附甲素葡萄糖醛酸苷和关附甲素硫酸酯:经MS-MS鉴定出m/z 606特征子离子m/z 177和m/z 430,进一步确证大鼠胆汁中存在关附甲素葡萄糖醛酸苷.结论:大鼠胆汁中存在Ⅰ相代谢产物关附壬素,以及Ⅱ相结合物关附甲素葡萄糖醛酸和硫酸结合物、关附壬素葡萄糖醛酸和硫酸结合物.     

汉黄芩素在FVB小鼠体内的磺酸化代谢特征研究

目的探讨汉黄芩素Ⅱ相代谢中主要的磺酸化代谢反应特征。方法采用FVB小鼠肠灌流模型及FVB小鼠肝脏S9体外反应体系,通过采用高效液相色谱-质谱法(HPLC-MS/MS)和高效液相色谱-二极管阵列检测器(HPLC-DAD)测定汉黄芩素及其代谢产物,研究汉黄芩素主要的Ⅱ相代谢反应之一磺酸化代谢反应的特征。结果汉黄芩素在FVB小鼠小肠均发生葡萄糖醛酸化与磺酸化代谢反应,其中磺酸化代谢产物的排出速率为[(3.46±0.16)nmol/30 min/10 cm]。而汉黄芩素在结肠中只检测出磺酸化代谢产物,其排出速率为[(1.40±0.24)nmol/30 min/10 cm]。体外试验显示,汉黄芩素的磺酸化代谢符合双相酶代动力学特征,由两种磺酸化转移酶(Sult)亚型介导。结论汉黄芩素的磺酸化代谢反应是汉黄芩素肠道代谢的重要组成部分,其在肝脏的磺酸化代谢由两种Sult酶催化完成。     

城南细辛化学成分研究(Ⅰ)

目的研究城南细辛的活性化学成分.方法利用柱层析方法分离化合物,理化性质以及光谱方法(UV、IR、NMR、MS)鉴定化合物.结果从城南细辛中离分得3个化合物,鉴定为1-细辛脂素(Ⅰ),1-芝麻脂素(Ⅱ)和β-谷甾醇(Ⅲ).结论化合物Ⅰ、Ⅱ、Ⅲ均为首次从该植物中分离得到.     

甲氨蝶呤联合米非司酮治疗未破裂异位妊娠68例的疗效观察

目的观察甲氨蝶呤(下称MTX)联合米非司酮治疗未破裂异位妊娠的疗效。方法2004年1月～2006年1月我院对168例未破裂的异位妊娠病例进行分析,随机分成Ⅰ、Ⅱ、Ⅲ组。Ⅰ组采用MTX50mg/m2每隔3d静脉注射1次,共2次;Ⅱ组采用MTX50mg/m2每隔3d分臀深部肌肉注射1次,共2次;Ⅲ组在Ⅱ组的方案上每天加服米非司酮100mg1次,共3次。结果Ⅰ组成功率为72%(36/50),Ⅱ组成功率为82%(41/50),Ⅲ组成功率为94.12%(64/68),Ⅰ、Ⅲ组间差异有显著性(P<0.01),Ⅰ、Ⅱ组间及Ⅱ、Ⅲ组间差异有明显性(P<0.05)。结论使用MTX50mg/m2隔3d肌注2次比隔3d静注2次效果好,而在Ⅱ组方案上同时加用米非司酮的治疗方案比Ⅰ、Ⅱ组方案的疗效更好。     

妊娠期糖尿病并发子痫前期的期待治疗时限及妊娠结局探讨

目的探讨妊娠期糖尿病并发子痫前期期待治疗时限及母儿预后结局。方法回顾性分析2005年1月至2008年12月,郑州市妇幼保健院收治的36例妊娠合并糖尿病并发子痫前期的孕妇(Ⅰ组),随机抽取无其他合并症的子痫前期(Ⅱ组)及妊娠期糖尿病(Ⅲ组)各40例,比较保胎天数及终止妊娠周数及终止妊娠结局。结果Ⅰ组与Ⅱ组比较,保胎天数及终止妊娠周数、妊娠结局差异无统计学意义。Ⅲ组的保胎天数及终止妊娠周数、妊娠结局与Ⅰ组和Ⅱ组相比较差异有统计学意义(P<0.05)。结论妊娠期糖尿病并发子痫前期期待治疗时限应在控制血糖基础上以子痫前期病情发展为终止妊娠的指标,采取个体化原则,严密监护下不超过2周为宜。     

妊娠高血压综合征患者外周血P-选择素的表达

目的探讨妊娠高血压综合征患者外周血P-选择素的表达与意义。方法用流式细胞术检测30例妊娠高血压综合征患者、20例正常妊娠者与15例正常人外周血P-选择素表达。结果妊娠高血压综合征患者外周血P-选择素表达为(18.63±8.92)%,明显高于正常妊娠组(3.25±1.73)%(P<0.01)和正常对照组(2.78±1.04)%(P<0.01)。结论妊娠高血压综合征患者存在P-选择素的高度表达。     

灯盏花素对大鼠急性肝细胞损伤的保护作用

目的探讨灯盏花素对大鼠急性肝损害的保护作用。方法取Wistar大鼠18只,随机分为Ⅰ、Ⅱ、Ⅲ3组各6只。胶原酶原位灌流法分离大鼠肝细胞后于Ⅰ、Ⅱ、Ⅲ组分别加入PBS 20mmol/L、LPS 3mg/L、LPS 3mg/L+灯盏花素20mmol/L,于施加因素后2、4、6、8、12、24h分别收集肝细胞和肝细胞培养液进行各指标测定。用透射电镜观察肝细胞形态学变化,用Fura-2-AM测定细胞内游离钙离子浓度,用[3H]油酸标记的生物膜法测定分泌型磷脂酶A2(secretory phospholipase A2,sPLA2),用Elisa法检测前列腺素E2(PGE2)的活性。结果Ⅱ组凋亡细胞与坏死细胞数均多于Ⅰ、Ⅲ组,差异均有统计学意义(P<0.01)。LPS加入肝细胞培养液2h、8h,Ⅱ组大鼠肝细胞中Ca2+浓度高于Ⅰ、Ⅲ组(P<0.05);Ⅱ组sPLA2、PGE2水平均高于Ⅰ组、Ⅲ组,差异均有统计学意义(P<0.01)。结论灯盏花素能显著抑制急性肝损害,可能与其对钙的拮抗和对sPLA2的抑制作用有关。     

白水茶中二种新黄酮甙的结构

从广西野生的白水茶(Camellia sinensis L.)中分得三种黄酮类成分:Ⅰ,Ⅱ和Ⅲ。经理化常数测定、光谱分析和化学反应鉴定:Ⅰ为已知成分芹菜素(apigenin),Ⅱ为芹菜素-5-O-α-L-吡喃鼠李糖基(1→4)-6″-O-乙酰基β-D-吡喃葡萄糖甙,Ⅲ为芹菜素-5-O-α-L-吡嘀鼠李糖基(1→4)-β-D-吡喃葡萄糖甙。Ⅱ和Ⅲ为首次报道的新黄酮甙,暂分别命名为山茶甙A(camellianin A)和山茶甙B(camcllianin B)。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.