新疆传统发酵乳酪乳清对高脂血症大鼠调血脂作用机制的研究

目的：探讨新疆哈萨克族传统发酵乳酪乳清（简称乳酪乳清）调节血脂的作用机制。方法：高脂乳剂灌胃制备高脂血症大鼠模型,以普伐他汀（20 mg?kg-1）作为阳性对照,观察乳酪乳清(50,100 mg?kg-1）对大鼠血清中胆固醇（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）和一氧化氮（NO）水平以及羟自由基（?OH）的清除能力和血浆胆固醇卵磷脂酰基转移酶（LCAT）活性的影响。结果：与高脂模型组相比,高、低剂量乳酪乳清组均可显著降低高脂血症大鼠血清中TC,TG,LDL-C,HDL-C的水平（均为P＜0.01）,增加NO含量（P＜0.05）,增强?OH的清除能力（P＜0.01）,提高LCAT的活性（P＜0.01）。结论：乳酪乳清可调节血脂水平,其机制可能与其升高HDL-C水平、增强胆固醇卵磷脂酰基转移酶酶活性以及清除?OH有关。     

螺旋藻激酶对动脉粥样硬化模型大鼠血管内皮功能的影响

目的:研究螺旋藻激酶(SPK)对动脉粥样硬化模型大鼠血管内皮功能的影响。方法:将60只大鼠随机分为正常对照组(蒸馏水)、模型组(蒸馏水)、阳性对照组(辛伐他汀,0.005 g/kg)和SPK低、中、高剂量组(80、160、320 U/kg)。除正常对照组外,其余各组大鼠均复制动脉粥样硬化模型;同时,各组大鼠ig相应药物,每天1次,连续给药12周。测定大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素6(IL-6)和肿瘤坏死因子α(TNF-α)的含量;苏木精-伊红染色观察大鼠胸主动脉血管内膜的形态改变。结果:与正常对照组比较,模型组大鼠血清中TC、TG、LDL-C、IL-6和TNF-α含量增加(P<0.01),HDL-C含量降低(P<0.01);血管内皮细胞脱落,内膜增生、向管腔内突起,平滑肌细胞增殖且排列紊乱,中膜弹力纤维崩解断裂。与模型组比较,各给药组大鼠血清中TC、TG、LDL-C、IL-6和TNF-α含量下降(P<0.05或P<0.01),阳性对照组和SPK中、高剂量组大鼠血清中HDL-C含量增加(P<0.05);给药组大鼠血管内皮细胞形态较模型组明显改善,其中SPK中、高剂量组大鼠血管内皮细胞各层结构完整、内膜基本光滑,SPK中剂量组大鼠血管中膜平滑肌细胞排列稍紊乱,与正常对照组比较无明显变化。结论:SPK有明显的降脂和抗炎作用,可保护血管内皮功能;其作用机制可能与降低血清中TC、TG、LDL-C、IL-6、TNF-α含量和升高血清中HDL-C含量有关。     

阿魏酸和川芎挥发油对大鼠实验性高脂血症的不同影响

目的:研究阿魏酸和川芎挥发油对大鼠实验性高脂血症的影响。方法:大鼠食用高脂饲料的同时,灌胃阿魏酸50 mg·kg~(-1)·d~(-1)或川芎挥发油100μl·kg~(-1)·d~(-1)。实验第0天和第30天检测大鼠血清中总胆固醇(TC),甘油三脂(TG),高密度脂蛋白-胆固醇(HDL-C)和低密度脂蛋白-胆固醇(LDL-C)水平。RT-PCR检测心肌中转化生长因子β1(TGF-β1)的mRNA表达。结果:阿魏酸明显降低大鼠血清中TC和LDL-C水平(P<0.05),川芎挥发油明显升高大鼠血清中TC水平(P<0.01)和LDL-C水平(P<0.05)。RT-PCR结果显示心肌中TGF-β1mRNA表达与血清中TC水平呈正相关(r=0.9265,P<0.05)。川芎挥发油能显著增加心肌TGF-β1mRNA的表达(P<0.05)。结论:阿魏酸具有降低血脂的作用,而川芎挥发油具有升高血脂的作用,其作用机制可能与影响心肌TGF-β1表达有关。     

番茄红素对高脂血症模型大鼠脑血管和神经元的保护作用

目的研究番茄红素对高脂血症所致脑血管和神经元损伤的保护作用。方法 SD大鼠在饲喂高脂饮食的同时每天ig给予番茄红素5,25,45,65,85,105和125 mg·kg~(-1),同时设正常对照组、高脂模型组和氟伐他汀钠10 mg·kg~(-1)组,实验期4周。用试剂盒检测血清和脑总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、氧化型低密度脂蛋白(Ox-LDL)、总抗氧化能力(T-AOC)、白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、血管细胞黏附分子1(VCAM-1)、血管内皮生长因子(VEGF)和一氧化氮(NO)水平;Western蛋白印迹法检测脑组织密封蛋白5、胶质纤维酸性蛋白(GFAP)和磷酸化P38蛋白(p-P38)水平;尼氏染色观察海马CA1和CA3区神经元形态变化并对其计数;高效液相色谱法检测血清番茄红素浓度。结果实验第4周末,与高脂模型组相比,番茄红素25～85 mg·kg~(-1)组血清和脑TC,TG,LDL-C,Ox-LDL,IL-1,TNF-α,VCAM-1,VEGF及脑NO,GFAP,p-P38水平降低(P<0.01),血清T-AOC,NO及脑密封蛋白5水平和脑海马区神经元数升高(P<0.01),105和125 mg·kg~(-1)组仅血清TC,TG,LDL-C及血清和脑IL-1,TNF-α水平降低(P<0.05),血清NO水平升高(P<0.01)。番茄红素干预剂量与血清番茄红素浓度呈二次曲线关系(P<0.01),其中65和85 mg·kg~(-1)组血清番茄红素浓度高于其他各组(P<0.01)。结论番茄红素主要通过影响血液中胆固醇水平以减少Ox-LDL生成,减轻炎性反应,减轻对血管内皮的损伤,维护血脑屏障通透性,间接降低星型胶质细胞活化程度,减少脑P38蛋白磷酸化及IL-1,TNF-α和NO分泌,发挥脑血管和神经元保护作用。     

共轭亚油酸对ApoE~(-/-)小鼠动脉粥样硬化炎症反应的影响

目的研究共轭亚油酸降低血脂及抑制动脉粥样硬化炎症反应的作用。方法将45只Apo E-/-小鼠按空腹体质量随机分为3组:(1)共轭亚油酸组,给予含2%共轭亚油酸的高脂饲料;(2)高脂模型组,给予单纯高脂饲料;(3)普通对照组,给予普通饲料。干预12周后,检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)水平,采用酶联免疫吸附试验(ELISA)法测定小鼠血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10水平。结果 (1)共轭亚油酸组血清TC、TG水平与高脂模型组相比显著降低高(P<0.05),HDL-C水平差异无统计学意义(P>0.05);(2)共轭亚油酸组血清TNF-α、IL-1β水平与高脂模型组相比显著降低(P<0.05),而IL-10则显著升高(P<0.05)。结论共轭亚油酸具有降低血脂和抗动脉粥样硬化炎症反应的作用。     

灵仙新苷对高脂血症大鼠早期动脉粥样硬化的干预作用

目的:研究灵仙新苷(clematichinenoside AR)调节血脂及抗动脉粥样硬化的作用。方法:采用高脂饲料喂饲和腹腔注射维生素D3结合腹腔注射LPS建立大鼠动脉粥样硬化模型,造模成功后灌胃给予高、中、低剂量的AR(32,16,8 mg.kg-1.d-1),8周后测定大鼠血清胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)、肿瘤坏死因子(TNF-α)、一氧化氮(NO)及诱导型一氧化氮合酶(iNOS);取其胸主动脉进行油红O染色,观察大鼠胸主动脉内膜脂质沉积情况;取肝脏进行常规HE染色,观察肝脏病变。结果:AR高、中剂量组能显著降低高血脂症大鼠血清TC,TG,LDL-C,TNF-α,NO水平和iNOS活力,升高HDL-C水平,差异具有统计学意义(P<0.05)。同时,AR能减少主动脉内皮脂质沉积,改善肝脏的脂肪变性和炎症细胞浸润。结论:AR具有调节血脂,减轻动脉粥样硬化发生和发展的作用,该作用与其调节NO及其合酶的形成和表达相关。     

海洋活性物质2,3-吲哚醌对实验性高脂血症的预防作用

目的通过实验性动脉粥样硬化动物模型,观察2,3-吲哚醌(2,3-dioxoindoline,MW147)预防用药时的调血脂作用。方法雄性鹌鹑喂饲高脂饲料,各用药组药物同时灌胃给药,连续用药8周,于用药第2,5,8周末测定血清脂质含量。结果MW14720,60,120mg·kg-1均可显著降低鹌鹑血清胆固醇、甘油三酯水平(P<0.05,P<0.01),对血清低密度脂蛋白和载脂蛋白B的升高也有程度不等的抑制作用(P<0.05,P<0.01)。MW147也可提高血清高密度脂蛋白和载脂蛋白A的水平(P<0.05,P<0.01)。结论MW147对实验性高脂血症有预防作用。     

葡萄籽原花青素及其组合物对家兔实验性动脉粥样硬化的抑制作用

目的 研究葡萄籽原花青素及其组合物对家兔实验性动脉粥样硬化的抑制作用。 方法 喂养高脂饲料建立实验性动脉粥样硬化家兔模型,实验分为正常对照组、模型组、原花青素组、原花青素与茶多酚组合物组、原花青素与姜黄素组合物组和辛伐他汀组;造模成功后灌胃给药4周,取血测定血脂水平,然后麻醉,取肝脏和部分主动脉做透射电镜检查和油红O脂肪染色。结果 原花青素及其组合物可显著降低动脉粥样硬化家兔血清甘油三酯、总胆固醇和低密度脂蛋白水平;显著减轻血管内皮损伤,减轻血管和肝脏的脂滴沉积。结论 原花青素及其组合物通过保护血管内皮细胞和降低血管的脂质沉积发挥抗动脉粥样硬化作用。     

南极磷虾油对高脂血症大鼠血脂和抗氧化力的影响

目的探讨南极磷虾油对实验性高脂血症大鼠血脂和抗氧化力的影响。方法高脂饲料建立高脂血症大鼠模型,分别灌胃50,100和500 mg.kg-1南极磷虾油,连续30 d,测定大鼠血清总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)、血清一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)以及丙二醛(MDA)水平。结果南极磷虾油能显著降低高脂血症大鼠血清中的TC、TG和LDL-C含量,降低动脉粥样硬化指数(AI)。提高大鼠血清中NO含量,提高SOD和GSH-PX活性,降低MDA含量。结论南极磷虾油对高脂血症大鼠具有调血脂的作用和抗氧化作用,其抵抗动脉粥状硬化方面的作用优于深海鱼油。     

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.     

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.     

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.