南瓜多糖对糖尿病大鼠胰岛Fas、Fas-L、Bcl-2及Bax表达的影响

目的观察南瓜多糖(PP)对链脲佐菌素(STZ)诱导的糖尿病大鼠胰腺组织中Fas、Fas-L、Bcl-2及Bax表达的影响。方法建立链脲佐菌素性糖尿病模型,PP(150、300、600mg.kg-1)灌胃进行治疗。3wk后检测大鼠空腹血糖值;采用免疫组化的方法探讨PP对链脲佐菌素性糖尿病大鼠Fas和Fas-L蛋白表达的影响;采用RT-PCR的方法观察PP对实验性糖尿病大鼠胰岛凋亡调控基因Bax和Bcl-2表达的影响。结果PP(300、600mg.kg-1)能明显降低STZ诱导的糖尿病大鼠的空腹血糖值;PP(150、300、600mg.kg-1)治疗后大鼠胰腺组织中Fas/Fas-L蛋白的表达率明显低于STZ模型组;PP(150、300、600mg.kg-1)给药3wk后,大鼠Bcl-2基因的表达明显增加,PP(300、600mg.kg-1)治疗后大鼠Bax基因的表达明显下降,Bcl-2与Bax的比值明显增加。结论PP对实验性糖尿病大鼠有降血糖作用,其作用与降低大鼠胰腺组织中Fas、Fas-L蛋白的表达、调节Bcl-2与Bax基因的表达有关。     

格列齐特联合二氢杨梅素对糖尿病大鼠的作用研究

目的:研究格列齐特联合二氢杨梅素对链脲佐菌素(STZ)诱导的糖尿病模型大鼠控制血糖、胰岛和胰岛 β 细胞的有效性.方法:成年雄性Wistar大鼠单次腹腔注射STZ(45 mg·kg-1)诱发糖尿病,连续3周给糖尿病大鼠灌胃格列齐特(GLZ,10 mg·kg-1)、二氢杨梅素(DHM,50 mg·kg-1)或两者合用.实...     

桑叶总黄酮对2型糖尿病大鼠胰岛β细胞氧化损伤的影响

目的观察桑叶总黄酮对2型糖尿病大鼠胰岛β细胞氧化损伤的影响及作用机制。方法给大鼠腹腔注射30 mg·kg-1链脲佐菌素,建立2型糖尿病动物模型。造模后随机分成模型组,桑叶总黄酮低、中、高剂量组(50,100,150 mg·kg-1)和罗格列酮组(1.8 mg·kg-1),另取正常大鼠作为对照组,每组均为10只。灌胃给药,每日1次,连续5周后测定大鼠血清空腹血糖(FBG)、空腹胰岛素(FINS)水平和胰腺组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)含量。免疫组化法检测Bcl-2、Bax蛋白的表达,末端脱氧核糖核酸缺口标记法(TUNEL)加免疫组化法测定胰岛β细胞凋亡率。结果桑叶总黄酮能显著降低胰腺组织MDA水平,提高SOD和GSH-Px水平(P<0.05或P<0.01),显著上调抗凋亡基因Bcl-2表达,下调促凋亡基因Bax表达(P<0.05或P<0.01),使胰岛细胞凋亡率显著降低(P<0.05或P<0.01),并能显著降低FBG水平,升高FINS含量(P<0.05或P<0.01),其中以150 mg·kg-1桑叶总黄酮最为明显。结论桑叶总黄酮对2型糖尿病大鼠具有较好的抗氧化作用,可以缓解胰岛β细胞凋亡的发生。     

苦荞提取物对2型糖尿病大鼠胰岛细胞凋亡的干预作用

目的：探讨苦荞提取物对2型糖尿病大鼠胰岛细胞凋亡的干预作用.方法：Sprague-Dawley大鼠分为6组：正常对照组、模型组、二甲双胍组、苦荞提取物低、中、高剂量组.模型组和给药组采用高脂高糖诱导饮食.两周后,腹腔一次性注射链脲佐菌素（STZ,30 mg·kg^-1）建立大鼠2型糖尿病模型.二甲双胍组给予300 mg·kg^-1剂量灌胃,苦荞提取物组分别给予250 mg·kg^-1、500 mg·kg^-1、1 g·kg^-11苦荞提取物灌胃.给药4周后,检测大鼠空腹血糖值和空腹血清胰岛素（FINS）值,处死大鼠,取大鼠胰脏组织,H＆amp;E染色观察形态学变化;TUNEL法观察胰岛细胞凋亡;免疫组织化学法检测细胞死亡信号转导效应酶caspase-3在胰岛中的表达.结果：与模型组比,苦荞提取物组可显著降低大鼠空腹血糖值和空腹FINS值（P〈0.05）.HE结果显示苦荞提取物组和二甲双胍组大鼠胰岛形态未出现明显缩小及胰岛细胞减少情况,TUNEL结果显示苦荞提取物组与二甲双胍组胰岛中胰岛细胞凋亡均明显减少,caspase-3结果显示苦荞提取物组和二甲双胍组中caspase-3表达均有下调趋势（P〈0.05）.结论：苦荞提取物能够有效降低STZ诱导2型糖尿病大鼠胰岛细胞的凋亡.     

大豆异黄酮对2型糖尿病大鼠血清中SOD MDA GSH及NO的影响

目的研究大豆异黄酮对2型糖尿病大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)及一氧化氮(NO)的影响。方法以高脂饲料喂养后的雄性SD大鼠腹腔注射小剂量链脲佐菌素(STZ)诱导2型糖尿病模型。将实验动物随机分为普食对照组、糖尿病对照组、大豆异黄酮250mg/kg、50mg/kg剂量干预组。检测各组喂养6周、10周的血糖水平,检测第10周后大鼠血清中SOD、MDA、GSH及NO的变化。结果与糖尿病对照组相比,大豆异黄酮250mg/kg剂量干预组大鼠血清中的SOD明显升高(P<0.05),MDA与NO明显下降(P<0.05);大豆异黄酮50mg/kg剂量干预组大鼠血清中GSH明显升高(P<0.05)。结论大豆异黄酮能改善2型糖尿病大鼠的抗氧化能力。     

酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响

目的:探讨酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响及其作用机制.方法:以高糖高脂饲料对SD大鼠饮食诱导6周,随后一次性i.p.给予链脲佐菌素(STZ)制备糖尿病大鼠模型.模型建立后,实验组给予酮替芬0.09 mg·kg-1·d-1,分别在第0、4、8周宰杀实验大鼠,检测空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR),检测炎症因子IL-6、TNF-α,并留取胰腺组织,制片染色进行光镜、电镜观察.分离胰岛细胞线粒体,检测细胞色素C氧化酶(Cytochrome C oxidase,CCO)、琥珀酸脱氢酶(Succinate dehydrogenase,SDH)活性.结果:酮替芬降低糖尿病大鼠的血糖水平(P＜0.05),增加ISI和降低HOMA-IR(P＜0.01),降低IL-6和TNF-α水平,增加胰腺组织中CCO和SDH活性(P＜0.01),还可以改善胰岛细胞形态结构.结论:酮替芬能改善糖尿病大鼠的胰岛功能,其作用机制可能是通过抑制NF-кB激活实现抗炎及改善β细胞线粒体的能量代谢.     

魔芋葡甘聚糖对链脲霉素致大鼠糖尿病的防治作用

目的:探讨魔芋葡甘聚糖(GMN)防治链脲霉素(STZ)所致大鼠糖尿病的作用及机制.方法:于Wistar大鼠腹腔注射50 mg·kg-1体重链脲霉素,建立糖尿病模型.分别于模型建立前后灌胃给予相同剂量的GMN,以血糖和尿糖及胰腺病理组织学检查为观察指标,同时检测肝匀浆超氧化物岐化酶(SOD)活性和过氧化脂质(LPO)含量以及血清淋巴因子IL-1和TNF-a水平.结果:GMN于模型建立前给药可明显降低糖尿病大鼠的血糖和尿糖值,停药后该作用可持续1周时间.与模型对照组相比,病理切片显示胰岛仅有少量的炎性细胞浸润,无明显的β细胞损伤.GMN预防给药可增高SOD活性,减少LPO含量,但对细胞因子无明显作用.结论:GMN预防给药可防止STZ诱导的大鼠糖尿病发生,作用持久,降糖作用与清除体内自由基从而减少β细胞损伤有一定相关性.     

糖尿病并发症相关性氧化应激的实验研究

目的链脲佐菌素(STZ)诱导大鼠1型糖尿病模型的基础上,探讨糖尿病氧化应激指标的变化。方法采用一次性腹腔注射STZ的方法,监测不同时点大鼠的空腹血糖、体质量及血浆中的丙二醛(MDA)和超氧化物歧化酶(SOD)等指标,并对结果进行统计学处理。结果大鼠注射STZ 72h后血糖值达到成模标准,并逐渐出现糖尿病表现,观察7周,始终满足成模标准,未见转复。DM组大鼠肾脏及肝脏肥大指数较CON组显著增加。氧化应激相关指标测定表明,较对照组相比,实验组大鼠血浆中脂质过氧化产物MDA水平显著升高,而SOD水平显著下降。结论本实验Ⅰ型糖尿病模型大鼠造模成功且模型稳定,氧化应激指标改变。     

链脲佐菌素致糖尿病小鼠模型的建立及抗氧化能力的影响

目的探讨一次性腹腔注射链脲佐菌素（Streptozocin,STZ）诱导糖尿病模型的最适剂量及成模小鼠机体抗氧化能力的改变。方法选80只小鼠随机分为4组：正常对照组、100mg·kg^-1、150mg·kg^-1、200mg·kg^-1 STZ 3个剂量组（M1、M2、M3）,采用一次性腹腔注射不同剂量STZ,7d后观察小鼠的造模成功率、死亡率、体重变化、空腹血糖及血清T-SOD、MDA值。结果随着一次性腹腔注射链脲佐菌素剂量的增加,小鼠体重减轻明显,空腹血糖值显著性升高（P〈0．01）,血清T-SOD值明显下降（P〈0．01）,血清MDA含量明显增加（P〈0．01）。结论一次性腹腔注射STZ 150mg·kg^-1时,小鼠成模率高、死亡率低、糖尿病模型稳定,为最适造模剂量;成模小鼠机体抗氧化能力较正常小鼠明显下降。     

1型糖尿病裸鼠模型的制作和成模后的注意事项

目的:探讨链脲佐菌素腹腔注射制作1型糖尿病小鼠模型的最佳剂量.方法:Balb/c裸鼠40只随机分为正常对照组(A组)及175、200、225 mg/kg链脲佐菌素组(B、C、D组).腹腔注射不同剂量链尿佐菌素诱导小鼠糖尿病作为动物模型.血糖仪检测小鼠血糖变化,光镜观察胰岛的组织学改变情况.结果:对照组血糖基本无变化,模型组血糖值随时间增加而增加.不同桌量链脲佐菌素诱导小鼠胰岛β细胞损伤的病理改变和程度均有所差异.结论:3种剂量链脲佐菌素均可诱导不同程度的1型糖尿病发生.以链脲佐菌素200mg/kg诱导的1型糖尿病的效果为最佳.     

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.     

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.     

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.