胆固醇结石患者肝脏核受体基因蛋白的表达

目的 探讨胆囊胆固醇结石(CGs)患者肝脏的核受体基因的蛋白表达.方法 对20例CGS(胆石组)和10例无胆石症的胆囊息肉患者(对照组)测定了胆石胆固醇成分及血清脂类成分:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和胆汁脂类成分(胆固醇、磷脂和胆汁酸),并计算胆汁总脂和胆汁胆固醇饱和指数.Western blot法测定肝脏肝受体同类物1(LRH-1)、法尼醇受体(FXR)、人类固醇异生物受体(SXR)及肝脏X受体a(LXRa)基因的蛋白表达量.结果 胆石组血清HDL-C浓度明显低于对照组[(0.91±0.05)mmol/L vs.(1.31±0.09)mmol/L](P<0.01);胆汁胆固醇摩尔百分比浓度较对照组高[(7.89±0.39)mol%vs.(5.15±0.89)mol%](P<0.01);胆汁总脂较对照组明显下降[(105.62±10.51)g/L vs.(153.50±13.20)g/L](P<0.05);胆石组LRH-1蛋白表达高于对照组[(0.88±0.05)vs.(0.69±0.03)3(P<0.05),LXRa、FXR和SXR表达两组差异无统计学意义(P>0.05).结论 人肝脏LRH-1的蛋白表达增高与胆囊胆固醇结石形成有关.     

脂质异常与胆囊胆固醇结石形成关系

目的探讨脂质异常与胆囊胆固醇结石形成的相互关系。方法对50例胆囊胆固醇结石患者（结石组）与30例对照组空腹静脉血血脂进行测定,同时收集新鲜胆囊胆汁化学法测定胆汁中胆固醇（CHD）,胆汁酸（TBA）及磷脂（PL）的含量并计算胆固醇饱和指数（CSI）,评价各指标间的关系。同时应用免疫组化方法检测CD68在50例胆固醇结石患者胆囊壁（结石组）和30例对照组标本中的表达。结果实验组血清中TC、TG、LDL值及胆汁中胆固醇、CSI、PL较对照组高,而HDL和胆汁中胆汁酸低于对照组,P〈0.05差异有统计学意义。结论脂质异常与胆结石的形成关系密切。     

成石胆汁组分及成核特性的研究

研究了22例胆囊胆汁的成分及成核特性。其中胆固醇混合性结石组9例，色素性结石组5例，对照组8例。结果显示：胆固醇混合性结石组胆囊胆汁中总胆盐减少，总胆盐中胆固醇溶解能力较强的胆盐的比例下降，胆汁脂类干重下降．卵磷脂相对升高，胆固醇单水结晶形成时间缩短；色素性结石组胆囊胆汁的总胆盐及脂质干重下降；各组胆囊胆汁胆固醇饱和度差异无显著性。     

阿嗪米特对豚鼠胆囊胆固醇结石的治疗作用

目的:研究阿嗪米特(azintamide)对豚鼠胆囊胆固醇结石的治疗作用。方法:用高胆固醇饮食诱发豚鼠胆囊胆固醇结石模型,进行胆囊结石计数;测定胆囊体积和胆囊胆汁量;测定血清总胆汁酸(TBA)、总胆红素(TBIL)、胆固醇(TCHO)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-C)、碱性磷酸酶(ALP);测定胆汁TCHO,TBA和TBIL。观察阿嗪米特(20和80mg·kg~(-1))对胆囊胆固醇结石的治疗作用。为探讨阿嗪米特抗胆囊胆固醇结石的作用机制,对胆囊壁组织进行了黏液素(mucin)的免疫组化实验。结果:与模型组比较,阿嗪米特20和80mg·kg~(-1)组成石率明显下降;胆囊体积和胆囊胆汁量显著减少;血清TCHO及LDL-C明显降低(P＜0．05);胆汁TBA升高(P＜0．05),胆汁TCHO及TBIL降低(P＜0．05)。黏液素免疫组化实验中可观察到,模型组黏液素表达水平较高,而阿嗪米特组黏液素表达水平较低。已知利胆药熊去氧胆酸(UDCA)亦有显著效果。结论:阿嗪米特对高胆固醇饮食诱发的豚鼠胆囊胆固醇结石模型具有明显的治疗作用。     

扶正利胆汤对贲门癌术后胆囊收缩障碍的临床疗效观察

目的 研究扶正利胆汤对贲门癌术后胆囊收缩障碍的临床治疗作用及其机制探讨.方法 选择120例贲门癌术后患者,随机分为试验组60例和对照组60例;试验组患者,在术后第10天开始口服扶正利胆汤,连服20天;对照组患者,在术后第10天口服等体积的水,连服20天;在实验治疗期间,对上述两组患者均进行常规抗炎、补液等治疗.所有患者分别于术前3天、术后30天对胆囊进行超声波指标测定,测定条件是空腹、服用脂餐0.5小时后、服用脂餐1小时后,应用超声波测定胆囊最大纵切面积、长径、短径,计算胆囊超声容积、排空率指标,并在术前3天、术后30天测定空腹血清胆囊收缩素浓度.比较两组患者手术前后胆囊的容积、排空、排空率及空腹血清胆囊收缩素浓度.结果 1）两组患者手术前后胆囊收缩功能比较：对照组患者术后胆囊容积较术前明显增大（P＜0.05）,治疗组患者术后胆囊容积较术前没有显著性改变;术前治疗组和对照组患者胆囊容积无显著差别（P＞0.05）;术后试验组胆囊容积比对照组患者的胆囊容积明显缩小,两组比较具有显著性差异（P＜0.05）.2）两组患者手术前后空腹血清胆囊收缩素（CCK）浓度比较：术前两组CCK浓度无明显差别（P＞0.05）;术后对照组患者CCK浓度较术前明显下降（P＜0.05）,治疗组患者术后CCK浓度较术前无明显改变（P＞0.05）,术后试验组患者较对照组血清CCK浓度明显升高,两组比较有显著性差异（P＜0.05）.结论 贲门癌术后出现胆囊排空障碍,术后胆囊容积与术前相比明显增大.扶正利胆汤可以提高血清CCK浓度,改善术后胆囊容积,对于贲门癌术后的胆囊收缩障碍有一定的治疗作用.     

缬栀提取物治疗胆囊凝结物的实验研究

目的： 观察缬栀提取物对胆囊凝结物的治疗作用。方法： 将24只大耳白家兔手术植入以胆固醇为主的凝结物，3 d后随机分为模型组、复方缬栀组和阳性对照组各8只。模型组以等体积0.9%氯化钠溶液灌胃，复方缬栀组以缬栀提取物1.2 g·kg 1(以生药计) 灌胃，阳性对照组以去氧胆酸13.8 mg·kg 1灌胃。连续用药75 d后，手术取出胆囊凝结物称重，测量胆固醇、总胆汁酸浓度以及胆囊壁组织学检查。结果：复方缬栀组、阳性对照组和模型组凝结物消失率分别为37.5%，25.0%，0.0%(P＜0.01)。复方缬栀组胆囊凝结物平均重量明显减轻，胆汁固形物含量及总胆汁酸水平明显升高，血清胆固醇含量明显下降，与模型组比较，均差异有显著性(P＜0.05～0.01)，与阳性对照组比较，差异无显著性(P＞0.05)；复方缬栀组胆囊组织基本正常，模型组呈明显炎症改变。结论：复方缬栀提取物对胆囊以胆固醇为主的混合凝结物有明显的治疗作用。     

缬草提取物对胆汁酸代谢及肝损伤影响的实验研究

［摘要］目的探讨缬草提取物对高胆固醇 高脂肪 高糖膳食所致的胆汁 胆汁酸代谢变化及肝损害的影响。方法①大耳白种家兔24只,随机分为3组,每组8只。治疗组和对照组给予高胆固醇 高脂肪 高糖饲料。治疗组每天灌胃缬草提取物30 mg&#8226;kg 1,对照组灌胃等容积0.9%氯化钠溶液,正常组自由进食标准颗粒饲料,同时每天灌胃等容积0.9%氯化钠溶液。观察实验兔的血清丙氨酸氨基转移酶（ALT）、血总胆固醇（TC）及总胆汁酸（TBA）含量、胆汁的流量及其TC 磷脂 TBA含量、胆囊结石形成情况、肝组织学检查以及主动脉壁粥样斑块观察。②Wistar大鼠24只,随机分为3组,每组8只。治疗组和对照组给予高胆固醇 高脂肪 高糖饲料,正常组自由进食基础饲料。治疗组每天灌胃缬草提取物50 mg&#8226;kg 1,对照组则每天灌胃等容0.9%氯化钠溶液。观察血清TC、TBA及肝组织学检查。结果①家兔治疗组胆总管胆汁流量及固形物含量较对照组显著增加（P＜0.01）,胆汁中的TBA含量明显增加（P＜0.05）,血清TBA较对照组明显降低（P＜0.05）,胆囊内凝结物形成率明显低于对照组（P＜0.05）、肝损伤较对照组显著减轻。②大鼠治疗组血清TBA较对照组降低（P＜0.05）,肝损伤较对照组减轻。结论缬草提取物可以增加胆汁中TBA含量,提高TBA/TC结石形成,降低血清TBA浓度,明显减轻肝损伤。     

熊去氧胆酸联合中药对胆囊结石家兔模型保胆取石术后胆汁酸 、胆固醇合成代谢的影响

目的 研究保胆取石术术后应用熊去氧胆酸联合中药对胆囊结石家兔模型术后胆汁酸、胆固醇合成代谢的影响.方法 选择雄性新西兰家兔60只为研究对象,建立胆囊结石模型后进行内镜下保胆取石术,根据术后处理方式不同分为3组,对照组给予普通饮食,模型组给予致石饮食,干预组给予致石饮食+熊去氧胆酸联合中药.检测3组家兔血清中胆固醇(TC)、总胆汁酸(TBA)、总胆红素(TBIL)含量以及胆固醇7-羟化酶(CYP7A1)和胆汁酸盐输出泵(BSEP)运输因子acbc11 mRNA含量.结果 干预后3周、5周时,模型组家兔血清中TC、TBIL含量高于对照组,TBA含量均低于对照组(t=3.571~24.374,P<0.05);干预组家兔血清中胆固醇TC、TBIL含量低于对照组,TBA含量均高于模型组(t=2.438~18.230,P<0.05);模型组家兔胆囊组织中CYP7A1和acbc11的mRNA含量低于对照组(t=11.369~20.096,P<0.05),干预组家兔胆囊组织中CYP7A1和acbc11的mRNA含量高于模型组(t=5.923~16.049,P<0.05).结论 熊去氧胆酸联合中药有助于修复受损胆固醇7-羟化酶和胆汁酸盐输出泵运输因子acbc11基因表达,调节胆汁酸、胆固醇、胆红素的代谢水平,预防保胆取石术后结石复发.     

成石胆汁组分成核特性的研究

研究了２２例胆囊胆汁的成分及成核特性。其中胆固醇混合性结石组９例，色素性结石组５例，对照组８例。结果显示：胆固醇混合性结石组囊胆汁中总胆盐减少，总胆盐中胆固醇溶解能力较强的胆盐的比例下降，胆汁脂类干重下降，卵磷脂相对升高，胆固醇单水结晶形成时间综合蛞；系性结石组胆囊胆汁的胆盐及脂质干重下降；各组胆囊胆汁胆固醇饱和度差异无显性。     

银杏叶提取物对血管性痴呆小鼠大脑皮层生长抑素及胆囊收缩素表达的影响

目的 观察银杏叶提取物(EGB)对血管性痴呆(VD)小鼠大脑皮层生长抑素(SS)和胆囊收缩素(CCK)表达的影响,探讨EGB对VD的改善作用.方法 复制VD小鼠模型,利用Y-迷宫检测VD模型小鼠学习记忆能力及不同剂量EGB治疗组的改善作用,实时定量聚合酶链式反应(PCR)方法检测各组动物大脑皮层中生长抑素和胆囊收缩素mRNA的变化,免疫组织化学方法研究不同剂量EGB对VD小鼠大脑皮层生长抑素和胆囊收缩素阳性神经元数量的影响.结果 各试验组小鼠均比对照组小鼠Y-迷宫学习记忆训练次数明显增多(P＜0.05),高低剂量EGB治疗组迷宫学会次数与模型组相比明显减少,且高剂量治疗组减少更明显(P＜0.05).VD模型组小鼠大脑皮层生长抑素和胆囊收缩素mRNA转录水平与对照组相比显著下调,高低剂量EGB治疗组与VD模型组相比显著上调(P ＜0.05);VD模型组小鼠大脑皮层生长抑素和胆囊收缩素阳性神经元数量与对照组相比显著减少,高低剂量EGB治疗组与VD模型组相比显著增多(P＜0.05).结论 EGB通过增加大脑皮层中生长抑素和胆囊收缩素的表达,对VD小鼠的学习记忆能力可起到一定的改善作用.     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.