HPLC法同时测定重酒石酸去甲肾上腺素注射液和盐酸去氧肾上腺素注射液的含量及有关物质

目的:建立测定重酒石酸去甲肾上腺素注射液和盐酸去氧肾上腺素注射液含量及有关物质的方法.方法:采用高效液相色谱法,色谱柱:Kromasil C18色谱柱(4.6 mm×250 mm,5 μm);流动相:甲醇-乙腈-庚烷磺酸钠溶液(1∶1∶8);检测波长:280 nm;流速:1 ml/min;柱温:30 ℃.结果:重酒石酸去甲肾上腺素在80～320 μg/ml范围内与峰面积呈良好的线性关系,r=0.999 8;高、中、低3种浓度的平均回收率为101.2%,RSD为0.18%(n=9).重酒石酸去甲肾上腺素的最小检测限为152.3 ng/ml.盐酸去氧肾上腺素在100～400 μg/ml范围内与峰面积呈良好的线性关系,r=0.999 6;高、中、低3种浓度的平均回收率为98.1%,RSD为0.051%(n=9).盐酸去氧肾上腺素的最小检测限为103.8 ng/ml.结论:该法简便、准确、灵敏度高,重现性好,可用于重酒石酸去甲肾上腺素注射液和盐酸去氧肾上腺素注射液的含量测定和有关物质检查.     

HPLC-ECD测定重酒石酸去甲肾上腺素的有关物质

目的:建立重酒石酸去甲肾上腺素有关物质的高效液相色谱-电化学检测方法(HPLC-ECD)。方法:采用TSK C18柱(150 mm×4.6 mm,5μm);以0.05%庚烷磺酸钠溶液(用磷酸调节pH至2.2)-乙腈(925∶75)为流动相,玻碳圆盘电极为工作电极,银-氯化银电极为参比电极,工作电位为+0.6 V。结果:去甲肾上腺素、肾上腺素、去甲肾上腺酮、多巴胺和2-氯-1-(3,4-二羟基苯基)乙酮均在0.05～5μg·mL-1浓度范围内线性关系良好,相关系数分别为0.9998,0.9999,1.0000,0.9999,0.9994(n=7);检测限分别为0.07,0.07,0.08,0.1和0.2 ng(S/N≥3)。4种有关物质的平均加样回收率为97.2%,100.4%,98.2%,103.1%;RSD为1.6%,1.5%,1.3%,2.8%(n=6)。结论:采用高效液相色谱-电化学检测法测定重酒石酸去甲肾上腺素有关物质,方法灵敏度高,选择性强,重现性好,能够用于重酒石酸去甲肾上腺素的质量控制。     

参附注射液降低难治性脓毒休克去甲肾上腺素依赖的研究

探讨参附注射液降低难治性脓毒休克患者对去甲肾上腺素剂量/时间依赖的有效性。选择2014年10月至2016年9月入住我院重症医学科的难治性脓毒休克患者80例,随机分为进行常规治疗的对照组和常规治疗加参附注射液治疗的观察组,比较2组患者使用去甲肾上腺素总剂量、输注去甲肾上腺素总持续时间、输注去甲肾上腺素剂量＞0.5 μg/（kg·min）持续时间,患者MAP达标时间、ICU住院时间、ICU住院死亡率。观察组患者输注去甲肾上腺素总持续时间显著低于对照组（P＜0.05）,2组患者输注去甲肾上腺素总剂量、MAP达标时间、ICU住院时间、ICU住院死亡率差异无统计学意义（P＞0.05）。参附注射液能够降低难治性脓毒休克患者对去甲肾上腺素的剂量/时间依赖,但不能降低患者ICU住院时间和ICU住院死亡率。     

HPLC-ECD法测定小鼠脑组织内去甲肾上腺素的含量

目的:建立小鼠脑内去甲肾上腺素含量的高效液相色谱-电化学（HPLC-ECD）测定方法。方法:小鼠脑组织采用70%高氯酸沉淀蛋白后,以HPLC-ECD法进行分析。使用汉邦lichrospher C₁₈色谱柱（250 mm×4.6 mm,5μm）,流动相为醋酸钾缓冲液-甲醇（95:5,pH 4.5）,流速为1.0 ml·min^-1,温度为25℃;电化学检测器电压为0.6 V,电流为100 nA,频率为0.05 Hz。结果:去甲肾上腺素在0.1～25μmol·L^-1范围内线性关系良好,日内、日间RSD分别小于7.81%和3.61%,回收率为75.05%,测得小鼠脑内去甲肾上腺素含量为（8.94±0.71）μg·g^-1。结论:该方法快速、准确,适用于小鼠脑内去甲肾上腺素的测定     

毛细管电泳法分离分析去甲肾上腺素等单胺类神经递质及肾上腺素

利用毛细管电泳法分离去甲肾上腺素 ,5 -羟色胺以及多巴胺三种单胺类神经递质以及肾上腺素。采用自由区带电泳法 ,4 0mmol/L硼砂缓冲液 2 0PSI气压进样 5s,定电压 2 0KV分离 12min。结果显示四种物质完全分离     

剖宫产术中预防性输注去甲肾上腺素对腰麻下母婴的影响

目的 探讨剖宫产术中预防性输注去甲肾上腺素对腰麻下产妇及胎儿的影响。方法 选择择期行剖宫产术的美国麻醉医师协会分级标准Ⅰ~Ⅱ级、单胎、足月初产妇160例，随机分为2组（n=80）：去甲肾上腺素组和去氧肾上腺素组。当鞘内注射局麻药时2组分别静脉持续输注0.05 μg·kg^-1·min^-1去甲肾上腺素或0.5 μg·kg^-1·min^-1去氧肾上腺素，当收缩压（systolic blood pressure，SBP）>140 mmHg时停药。连续监测SBP、舒张压（diastolic blood pressure，DBP）、心率（heart rate，HR）、心输出量（cardiac output，CO）及外周血管阻力（systemic vascular resistance，SVR）及胎心情况。胎儿娩出后采集脐动脉血样行血气分析及新生儿Apger评分。记录产妇和胎儿不良反应的发生情况（低血压、窦性心动过缓、恶心呕吐及胎儿窘迫等）。结果 切皮（t₂）和胎儿娩出后即刻（t₃）时间去甲肾上腺素组SBP，HR及CO均高于去氧肾上腺素组，但SVR低于去氧肾上腺素组（P<0.05）；其他时间点2组间SBP、DBP、HR、CO及SVR比较差异无统计学意义。去甲肾上腺素组心动过缓发生率降低，但2组产妇低血压、恶心和呕吐发生率比较差异无统计学意义。2组胎儿脐动脉血pH值差异无统计学意义。结论 与去氧肾上腺素比较，预防性静脉输注去甲肾上腺素能够能更好地维持腰麻下产妇血压和CO，降低产妇心动过缓的发生率，但不能降低低血压、恶心和呕吐的发生率。     

肾上腺素与多巴胺治疗儿童脓毒性休克比较研究

目的：比较肾上腺素与多巴胺治疗儿童脓毒性休克的疗效。方法：采用前瞻性随机对照临床试验（RCT）研究方法,选择2013年2月至2015年2月入住我院PICU的脓毒性休克（给予充分液体复苏后仍存在低血压）的患儿60例,随机分为多巴胺组和肾上腺素组各30例并应用相应药物进行治疗。多巴胺起始剂量7.0 μg/（kg·min）,如未达到治疗目标,每20 min增加2.5 μg/（kg·min）,最大剂量20 μg/（kg·min）;肾上腺素起始剂量0.1 μg/（kg·min）,每20 min增加0.1 μg/（kg·min）,最大剂量0.3 μg/（kg·min）。比较两组患儿的血液动力学指标、氧代谢指标和病死率。结果：肾上腺素组平均动脉压（MAP）、射血分数（EF）、中心静脉血氧饱和度（ScvO2）、每小时尿量（UV）在用药后6 h、24 h均高于多巴胺组（P均<0.05）。两组患儿的心率（HR）、中心静脉压（CVP）在各时间点比较,差异均无统计学意义（P均>0.05）。肾上腺素组血清乳酸在用药后6 h高于多巴胺组（P<0.05）;在用药后24 h时,与多巴胺组比较,差异无统计学意义（P>0.05）。肾上腺素组病死率（16.67%）低于多巴胺组（40.00%）,差异有统计学意义（P<0.05）。结论：与多巴胺相比,肾上腺素能更有效纠正脓毒性休克患儿的血流动力学及氧代谢异常,早期应用能改善预后。     

中国药典“盐酸美他环素”原料药及其制剂有关物质测定方法的修改建议

目的改善盐酸美他环素原料药及其制剂中有关物质的药典标准规定.方法色谱柱Alltech Alltima C18(250×4.6 mm,5 μm);流动相0.05 mol/L草酸铵溶液-二甲基甲酰胺-0.2 mol/L磷酸氢二铵溶液(65277);流速1 ml·min-1;柱温35℃;检测波长为280 nm,进样量20 μl.结果除土霉素杂质外盐酸美他环素原料药及其制剂中尚含较多其他杂质.结论建议对盐酸美他环素原料药及其制剂药典方法中有关物质的标准规定予以修改.     

不同剂量去甲肾上腺素对高龄患者全麻诱导后血流动力学的影响

目的 观察静脉泵注不同剂量去甲肾上腺素对高龄患者全麻诱导后血流动力学的影响,探讨该药有效性和适宜剂量。方法 选取2018年8月至2020年2月在重庆大学附属肿瘤医院行全身麻醉的择期手术患者160例（年龄 ≥ 75岁）为研究对象,采用随机数字表法分为4组：A组（对照组）、B组[去甲肾上腺素0.025 μg/（kg·min）]、C组[去甲肾上腺素0.050 μg/（kg·min）]与D组[去甲肾上腺素0.075 μg/（kg·min）],每组40例。B组、C组、D组于麻醉诱导开始时刻分别以0.025 μg/（kg·min）、0.050 μg/（kg·min）、0.075 μg/（kg·min）速度静脉泵注去甲肾上腺素至切皮。A组于同期以同等速度静脉泵注生理盐水。4组分别于麻醉诱导前（T₀）、气管插管前（T₁）和气管插管即刻（T₂）,以及气管插管后1（T₃）、3（T₄）、5（T₅）、10分钟（T₆）和切皮即刻（T₇）,记录各时点血流动力学变化及心脏不良事件发生率,主要指标：全麻诱导后至切皮低血压的发生率;次要指标：全麻诱导后至切皮高血压和心动过缓的发生率。结果 4组患者不同时点收缩压（SBP）和舒张压（DBP）有随时间及分组的变化趋势,4组患者存在时间、组间及交互效应（P<0.05）,与A组比较,C组、D组SBP和DBP在T₁-T₇时点明显升高,差异有统计学意义（P<0.05）。4组患者不同时间点心率（HR）有随时间的变化趋势,4组患者存在时间效应（P<0.05）,无组间及交互效应（P>0.05）,与A组比较,B组、C组、D组HR在T₁-T₇时点无明显变化,差异无统计学意义（P>0.05）。C组、D组低血压发生率明显低于A组,差异有统计学意义（P<0.007 1）。4组患者高血压发生率、心动过缓发生率差异无统计学意义（P>0.05）。结论 持续静脉泵注去甲肾上腺素0.050 μg/（kg·min）和0.075 μg/（kg·min）对于预防高龄患者麻醉诱导后低血压是安全有效的。     

兰尼定对大鼠平滑肌细胞的肾上腺素能作用(英文)

电场刺激后释放的内源性去甲肾上腺素可引起大鼠输精管的双相收缩。初始的短暂收缩可被30μmol/L兰尼定和2μmol/L硝苯啶减弱,而后继的收缩部分可被2μmol/L硝苯啶消除,但被30μmol/L兰尼定增强。 外加的去甲肾上腺素也可产生输精管的双相收缩,这两相都能被2 μmol/L硝苯啶抑制,兰尼定30μmol/L可使两个相的收缩都减弱50％。我们推测兰尼定的结合位点在输精管的内质网。兰尼定对α-肾上腺素能刺激的不同相的作用不一致,表明对α-肾上腺素能的刺激一收缩偶合有两种方式。     

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.

---

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.

     

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.     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.