葛根芩连汤拮抗D-半乳糖诱导大鼠糖耐量减退作用

目的研究葛根芩连汤(gegenqinlian decoction,GGQLD)、二甲双胍(metformin,met)和水飞蓟宾(silibinin,sil)对D-半乳糖(D-galactose,G-gal)诱导大鼠糖耐量减退(impaired glucose tolerance,IGT)的影响.方法以ip D-gal 150 mg·kg-1,qd×56d诱导胰岛素抵抗(insulin resistance,IR),IGT大鼠模型,测其空腹血糖(fasting blood glucose,FBG)和口服葡萄糖耐量试验(o-ral glucose tolerance test,OGTT)后2小时血糖(2-hours blood glucose,2hBG)含量;并观察GGQL3个剂量、met和sil对病鼠FBG及OGTT后2hBG的效应.结果正常对照组、GGQL3个剂量、met和sil与模型组比较,FBG均未见明显影响,差异未见显著性(P＞0.05);而OGTT后2hBG,模型组明显高于正常对照组(P＜0.01),说明D-gal至大鼠IGT模型成立;GGQL3个剂量、met和sil均能抑制OGTT后2hBG的升高,差异均有高度显著性(P＜0.01),FBG与OGTT后2hBG间差值降低,差异均有高度显著性(P＜0.01),说明各药均能改善D-gal致IR模型大鼠的IGT.结论D-gal可诱导以IGT为表现的IR,其机制可能与D-gal诱导蛋白非酶糖基化-氧化应激-自由基损伤作用和直接干扰糖脂代谢有关;葛根芩连汤与met和sil一样,能改善D-gal诱导IR大鼠的糖耐量.     

葛根芩连汤对抗地塞米松诱导大鼠胰岛素抵抗作用

目的 研究葛根芩连汤时地塞米松(dexamethasone,DEX)诱导大鼠胰岛素抵抗模型动物糖耐量的效应,同时观察丙二醛(MDA)及超氧化物歧化酶(SOD)的影响,初步探讨其降低动物血糖的作用机制。方法 以DEX诱导胰岛素抵抗(insulinresistance,IR),糖耐量减退(IGT)大鼠模型,测其空腹血糖(FBG)和口服葡萄糖耐量试验(OGTT)后2 h血糖(2 hBG)以及给药后2 h空腹血清血糖(FSG)、SOD活性和MDA含量。结果 该方降低病鼠FBG和OGTT后2 hBG(P<0.01),改善DEX致IR模型大鼠的IGT;降低FSG(P<0.05),但对SOD和MDA无显著影响(P>0.05)。DEX抑制SOD的活性(P<0.01),并使MDA的含量升高(P<0.01)。结论 葛根芩连汤具有磺脲类药物的降糖作用。地塞米松致氧自由基清除受阻,导致机体脂质过氧化损伤,但方剂未显示对抗作用。     

葛根芩连汤对抗地塞米松诱导大鼠胰岛素抵抗作用

目的研究葛根芩连汤对地塞米松(dexamethasone,DEX)诱导大鼠胰岛素抵抗模型动物糖耐量的效应,同时观察丙二醛(MDA)及超氧化物歧化酶(SOD)的影响,初步探讨其降低动物血糖的作用机制.方法以DEX诱导胰岛素抵抗(insulinresistance,IR),糖耐量减退(IGT)大鼠模型,测其空腹血糖(FBG)和口服葡萄糖耐量试验(OGTT)后2 h血糖(2 hBG)以及给药后2 h空腹血清血糖(FSG)、SOD活性和MDA含量.结果该方降低病鼠FBG和OGTT后2 hBG(P＜0.01),改善DEX致IR模型大鼠的IGT;降低FSG(P＜0.05),但对SOD和MDA无显著影响(P＞0.05).DEX抑制SOD的活性(P＜0.01),并使MDA的含量升高(P＜0.01).结论葛根芩连汤具有磺脲类药物的降糖作用.地塞米松致氧自由基清除受阻,导致机体脂质过氧化损伤,但方剂未显示对抗作用.     

葛根芩连汤对2型糖尿病大鼠的降血糖抗氧化作用

目的 研究葛根芩连汤对2型糖尿病大鼠血糖的影响，同时观察动物体内氧化-抗氧化作用的变化。方法 以腹腔注射小量链脲霉素(SZT)后，加饲高脂、高热量饲料10周，造成糖耐量减退(IGT)、高脂血症、肥胖、高胰岛素血症、胰岛素敏感性低下和胰岛素抵抗（IR）的2型DM大鼠模型，测其空腹血糖征（FBG)和口服葡萄糖耐量试验(OGTT)后2小时血糖（2hBG)以及给药后2h空腹血清血糖(TSG)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果 该方降低痛鼠FBG和OGTT后2hBG(P＜0．01)，改善2型DM模型大鼠的IGT；降低FSG(P＜0.01)和MDA，提高SOD的活性(P＜0．01)。结论 葛根芩连汤能产生磺脲类或双胍类药物的降糖和改善糖耐量作用，并具有抗氧化活性．     

茵陈蒿汤改善地塞米松致大鼠胰岛素抵抗作用的实验研究

目的研究茵陈蒿汤对地塞米松(DX)致胰岛素抵抗(insulin resistance,IR)模型大鼠血糖、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性的影响.方法以DX致IR、糖耐量减退(IGT)模型大鼠分别ig药物或蒸馏水(DW)qd×7～8d,测定其空腹血糖(FBG)、口服葡萄糖(10g/kg)试验(OGTT)后2小时血糖(2hBG)及给药后2h空腹血清血糖(FSG)、SOD活性和MDA浓度,并与格列齐特组对照.结果茵陈蒿汤不影响病鼠FBG(P>0.05),却能明显降低大鼠OGTT后2hBG(P<0.01),改善地塞米松致IR模型大鼠的IGT.降低给药后2h FSG(P<0.01),但对MDA浓度和SOD活性均未见明显影响(P>0.05).结论茵陈蒿汤和格列齐特均可改善胰岛素抵抗,两药的作用机制可能有所不同.     

茵陈蒿汤改善地塞米松致大鼠胰岛素抵抗作用的实验研究

目的　研究茵陈蒿汤对地塞米松 (DX)致胰岛素抵抗 (insulinresistance ,IR)模型大鼠血糖、丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活性的影响。方法　以DX致IR、糖耐量减退 (IGT)模型大鼠分别ig药物或蒸馏水 (DW) qd× 7～ 8d ,测定其空腹血糖 (FBG)、口服葡萄糖 (1 0 g/kg)试验 (OGTT)后 2小时血糖 (2hBG)及给药后 2h空腹血清血糖 (FSG)、SOD活性和MDA浓度 ,并与格列齐特组对照。结果　茵陈蒿汤不影响病鼠FBG(P >0 .0 5) ,却能明显降低大鼠OGTT后 2hBG(P <0 0 1 ) ,改善地塞米松致IR模型大鼠的IGT。降低给药后 2hFSG(P <0 .0 1 ) ,但对MDA浓度和SOD活性均未见明显影响 (P>0 .0 5)。结论　茵陈蒿汤和格列齐特均可改善胰岛素抵抗 ,两药的作用机制可能有所不同。     

甘草对抗D-半乳糖诱导大鼠糖尿病模型的实验研究

目的探讨甘草、二甲双胍和水飞蓟宾对D-半乳糖诱导大鼠糖尿病模型的作用。方法以腹腔注射D-半乳糖（150mg／kg，1次／d，共8周）诱导胰岛素抵抗（IR），选用长期腹腔注射5％D-半乳糖[150mg／（kg·d）]诱导IR形成大鼠糖尿病模型，并测定空腹血糖（FBG）、糖耐量试验（OGTT）后2h血糖（2hBG）含量和体重变化。结果空白对照组、甘草组、二甲双胍组和水飞蓟宾组与模型组比较，FBG均无明显差异（P〉0．05）；而OGTT后2hBG，模型组与空白对照组比较存在明显差异（P〈0．01）；甘草、二甲双胍和水飞蓟宾均使造模后各组的大鼠体重增加，并能降低糖尿病大鼠的血糖水平。结论甘草、二甲双胍和水飞蓟宾能有效地抑制D-半乳糖所致糖尿病大鼠的血糖水平。     

冬凌草甲素调节JAK2/STAT3/SOCS-1信号通路对糖耐量异常大鼠胰岛素抵抗的影响

目的 探讨冬凌草甲素(Oridonin, Ori)对糖耐量异常(impaired glucose tolerance, IGT)大鼠胰岛素抵抗(insulin resistance, IR)的影响及作用机制。方法 采用高脂饮食喂养联合链脲佐菌素注射法构建IGT大鼠IR模型,大鼠分为正常组(CT组)、IGT模型组(IGT组)、Ori组(10 mg·kg^-1·d^-1)、Ori+Colivelin(COL)组(10 mg·kg^-1·d^-1 Ori+2 mg/kg COL),每组6只。血糖检测仪测定空腹血糖(FPG)、葡萄糖耐量试验(OGTT)2 h血糖(2 hPG),ELISA试剂盒测定空腹胰岛素(FINS)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)含量,计算胰岛素抵抗指数(HOMA-IR),血液自动分析仪测定血清胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)水平,HE染色观察肝脏病理形态,Western blot验证附睾脂肪磷酸...     

荔枝核皂苷对地塞米松致胰岛素抵抗糖尿病大鼠血糖血脂的影响

目的研究荔枝核皂苷对地塞米松(DX)致胰岛素抵抗(insulin resistance,IR)大鼠血糖、血脂的影响.方法采用DX诱导IR大鼠模型,观察荔枝核皂苷和罗格列酮对病鼠空腹血糖(FBG)和口服葡萄糖耐量试验(OGTT)后2 h血糖(2hBG)以及给药后2h空腹血清血糖(FSG)、总胆固醇(TC)、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)、丙二醛(MDA),以及丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)活性等指标的影响.结果荔枝核皂苷改善DX致IR模型大鼠的IGT,降低OGTT后2h期BG和FSG(P＜0.05);并能显著降低病鼠TC、TG、LDL-C含量(P＜0.05-0.01),显著提高HDL-C含量(P＜0.05);抑制AST、ALT活性(P＜0.05),降低AST/ALT;加强SOD活性和降低MDA的含量(P＜0.01),增强抗氧化能力.结论荔枝核皂苷对DX致IR大鼠有降血糖、调血脂改善肝功能等的作用,显示抗氧化作用.     

六黄合剂对胰岛素抵抗大鼠糖耐量和血清胰岛素的影响

目的探讨六黄合剂对胰岛素抵抗大鼠糖耐量和血清胰岛素的影响。方法应用地塞米松致大鼠胰岛素抵抗(IR)模型,观察六黄合剂对大鼠血糖、血清胰岛素的变化。结果六黄合剂能够降低胰岛素抵抗大鼠口服葡萄糖耐量试验后2h血糖浓度(2hBG)和空腹血清胰岛素水平(FINS)(P<0.01)。结论六黄合剂可以改善葡萄糖耐量减退(IGT)和IR。     

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.     

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.