南极磷虾肽对去卵巢骨质疏松症小鼠肠钙吸收的改善作用研究

目的 研究南极磷虾肽(peptide from Antarctic krill,AKP)对双侧去卵巢骨质疏松症模型小鼠肠钙吸收的改善作用。方法 对9周龄雌性健康C57BL/6J小鼠进行双侧卵巢摘除手术,建立骨质疏松症模型,术后12周,随机分为假手术组(生理盐水)、模型对照组(生理盐水)、阳性对照组(阿伦磷酸钠,1 mg/kg.BW)、南极磷虾肽组(800 mg/kg.BW)。每天灌胃一次,连续灌胃90 d后,通过测定血清生化指标(PTH、1,25(OH)2D3、血钙及血磷)以及肠钙吸收通道基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平,研究了南极磷虾肽对去卵巢骨质疏松症小鼠肠钙吸收的改善及作用机制;并且通过骨密度和骨钙骨磷含量的测定,进一步验证了南极磷虾肽对肠钙吸收的改善作用。结果 血清结果表明,AKP能够显著抑制血清中PTH的水平,增加血清中1,25(OH)2D3的含量,维持血清中钙、磷稳定;qRT-PCR结果表明,AKP能显著上调十二指肠中激素1,25(OH)2D3的受体VDR以及肠钙吸收通道关键基因Trpv6、CaBP-d9k、PMCA1b的mRNA表达水平,增强去卵巢骨质疏松小鼠的肠钙吸收功能;骨密度和骨钙、骨磷结果表明,AKP能够显著增加模型组小鼠的骨密度及骨钙、骨磷含量,进一步验证了AKP能够增强机体对钙离子的吸收,从而增加骨矿化作用,增加小鼠的骨量。结论 南极磷虾肽能够改善去卵巢骨质疏松症小鼠的肠钙吸收作用,增加去卵巢小鼠的骨矿含量。     

绿原酸通过降低骨髓间充质干细胞凋亡抗绝经后骨质疏松的机制研究

目的 探讨绿原酸对绝经后骨质疏松（PMOP）大鼠的影响及其机制。方法 采用卵巢切除术构建PMOP大鼠模型,将建模成功大鼠分为去卵巢（OVX）组、绿原酸组、绿原酸+SB203580组,各10只;同时设置10只假手术组。比较各组大鼠骨密度,股骨骨微结构,血清雌二醇、碱性磷酸酶（ALP）水平,骨髓间充质干细胞（BMSCs）凋亡率,BMSCs中Runt相关转录因子2(Runx2)、锌指转录因子（Osterix）、ALP mRNA水平,BMSCs中p-p38MAPK/p38MAPK、Caspase3蛋白水平。结果 OVX组大鼠股骨内骨小梁大量缺失,骨密度、骨小梁数量、血清雌二醇、ALP水平、BMSCs中Runx2、Osterix、ALP mRNA水平、BMSCs中p-p38MAPK/p38MAPK蛋白水平低于假手术组,差异有统计学意义（P<0.05）;OVX组股骨骨小梁分离度、BMSCs凋亡率、Caspase3蛋白水平高于假手术组,差异有统计学意义（P<0.05）。绿原酸组大鼠股骨骨小梁基本恢复,骨密度、骨小梁数量、血清雌二醇、ALP水平、BMSCs中Runx2、Osterix、AL...     

穿心莲内酯促进骨折骨愈合作用机制的研究进展

骨折后的愈合状态直接影响患者的生活质量,如何提高骨折患者骨愈合效果是亟待解决的问题。穿心莲内酯是穿心莲中主要活性成分,可能通过促进成骨细胞增殖,抑制核因子κB（NF-κB）信号通路激活,激活Wnt/β-连环蛋白（Wnt/β-catenin）信号通路,调节护骨素/细胞核因子κB受体活化因子配基（OPG/RANKL）信号通路,调节成骨基因表达产物,改善软骨细胞功能,抑制雌激素相关受体α（ERRα）信号通路等多途径促使骨愈合。总结了穿心莲内酯促进骨折骨愈合作用及其作用机制,希望为穿心莲内酯的临床使用提供依据。     

金雀异黄酮酊对去卵巢骨质疏松大鼠OPG/RANKL/RANK通路的影响

目的观察金雀异黄酮酊对去卵巢骨质疏松大鼠骨密度、血清骨代谢生物标志物以及骨保护素(osteoprotegerin,OPG)、核因子κB受体活化因子(receptor activator of NF-κB,RANK)和破骨细胞分化因子(receptor activator of NF-κB,RANKL)表达的影响,探讨其抗骨质疏松的作用机制。方法将30只3月龄SD雌性大鼠随机分为假手术组、模型组和金雀异黄酮酊组,通过去卵巢法构建骨质疏松大鼠模型,给予金雀异黄酮酊外用喷涂,治疗8周后分别测定大鼠股骨骨密度,采用Elisa法检测血清骨碱性磷酸酶(ALP)、骨钙素(OC)及血清Ⅰ型胶原交联C-末端肽(S-CTX)等骨代谢生物标志物,采用Western Blot法检测OPG和RANKL蛋白表达水平。结果与假手术组比较,去卵巢组大鼠子宫质量、血清雌激素水平、股骨骨密度、血钙、血磷和OPG蛋白表达水平均降低,而体质量、ALP、OC、S-CTX和RANKL蛋白表达水平均升高,差异有统计学意义(P<0.05);采用金雀异黄酮酊治疗8周后,与模型组比较,金雀异黄酮酊组体质量、ALP、OC、S-CTX和RANKL蛋白表达水平降低,而子宫质量、血清雌激素水平、股骨骨密度、血钙、血磷和OPG蛋白表达水平均升高,差异有统计学意义(P<0.05)。结论金雀异黄酮酊可调节骨代谢,显著提高骨质疏松大鼠的骨密度,可能与调控OPG/RANKL/RANK通路蛋白表达水平有关。     

锶抗骨质疏松的作用机制研究

目的:综述锶抗骨质疏松的作用机制,为其临床应用提供参考。方法:以"骨质疏松症机制""锶""骨细胞""雷奈酸锶""Osteoporosis""Strontium""Strontium Ranelate"等为关键词,组合查询2005-2018年中国知网、万方数据、PubMed等数据库中的相关文献,对锶抗骨质疏松的作用机制及含锶的药物进行归纳总结。结果与结论:共检索到相关文献978篇,其中有效文献38篇。锶抗骨质疏松的作用机制包括结合钙离子敏感受体、上调转化生长因子水平、调节成骨相关标志物表达等促进骨细胞形成;调节核因子κB受体活化因子/核因子κB受体活化因子配体/骨保护素(RANK/RANKL/OPG)信号通路、调节κB抑制蛋白α(IκBα)等抑制破骨细胞分化;诱导间充质干细胞(MSCs)表达成骨相关基因、激活Wnt/β-catenin信号通路促进MSCs成骨分化;改善骨的微观结构,增强骨强度。临床常用含锶药物为雷奈酸锶,其具有促进骨形成和抑制骨吸收的双重作用,与其他治疗骨质疏松症的药物相比,雷奈酸锶具有良好的治疗效果。     

小檗碱促进骨再生的研究进展

小檗碱作为一种从传统中药中提取的天然异喹啉生物碱,具有预防骨质疏松、抗炎、降血糖等多种生物功效且副作用小。小檗碱不仅可以通过激活经典成骨信号通路Wnt/β-catenin和丝裂原活化蛋白激酶（MAPK）等有效促进干细胞成骨分化,还可以通过干扰核因子κB(NF-κB)受体活化因子配体（RANKL）与NF-κB受体活化因子（RANK）之间的结合,进而影响下游的信号通路如MAPK、NF-κB等抑制破骨细胞的分化,促进骨再生。本文对小檗碱促进骨再生的作用机制进行综述,旨在为骨再生的研究提供新的思路。     

骨质疏松症的药物治疗进展

骨微结构破坏及骨转换失衡是骨质疏松症发病的重要病理机制。目前骨质疏松症的治疗靶点主要集中在抑制破骨细胞活性及增强成骨细胞活性。新型骨吸收抑制剂包括核因子κB受体活化因子配体的单克隆抗体、新型选择性雌激素受体调节剂等。新型骨形成促进剂有骨硬化素单克隆抗体、甲状旁腺激素制剂及钙敏感受体拮抗剂等。此外,他汀类药物也被发现对骨代谢有一定作用。本文对骨质疏松症的治疗新药作一概述。     

骨化三醇治疗社区女性绝经后骨质疏松症的疗效及安全性

<正>由绝经引起的骨质疏松症称绝经后骨质疏松症(post-menopausal osteoporosis,PMOP),是绝经后妇女发生的以低骨的微观结构退化为特征,致使骨的脆性增加以及易于发生骨折的一种全身性骨骼疾病[1],主要表现为骨密度下降,骨微结构破坏和骨折危险性增加[2]。1,25(OH)2D3又名骨化三醇,是维生素D3的主要代谢产物,有研究证明,补     

T2DM女性患者绝经后骨密度和血清25(OH)D水平分析

目的 探讨2型糖尿病(T2DM)女性患者绝经后骨密度与血清25羟维生素D[25(OH)D]水平的关系.方法 检测276例绝经后T2DM女性患者的腰椎、股骨颈和全髋骨密度,据此将其分为骨量正常组(88例)、骨量减少组(98例)和骨质疏松组(90例).同时也测定了HbA1c、血钙、血磷、ALP和25(OH)D水平.分析骨密...     

益气活血壮骨方治疗气滞血瘀型原发I型骨质疏松症的临床研究

目的：探讨益气活血壮骨方对气滞血瘀型原发I型骨质疏松症患者临床疗效和不良反应的影响。方法： 选取2010年1月-2012年1月120例原发I型骨质疏松症患者,随机分为益气活血壮骨方组（研究组）、仙灵骨葆组（对照组）,每组60例。连续给药12周后检测骨密度、骨钙素、1,25 （OH2） D3 改变,临床症状改善及不良反应。结果： 研究组骨密度、骨钙素及1,25 （OH2） D3 含量高于对照组,临床症状改善优于对照组,差异有统计学意义（P〈0.05）。结论：益气活血壮骨方对气滞血瘀型原发I型骨质疏松症患者可抑制骨吸收,促进骨形成,从而阻止骨量丢失,改善临床症状。     

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.     

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.