UPLC-PDA法测定藏药翼首草不同药用部位中齐墩果酸和熊果酸的含量

目的:建立测定藏药翼首草不同药用部位中齐墩果酸和熊果酸含量的方法,并比较其不同部位之间的含量差异。方法:采用超高效液相色谱-光电二极管阵列检测器(UPLC-PDA)测定翼首草不同药用部位(全草、地上部位和地下部位)齐墩果酸和熊果酸含量。色谱柱为Acquity UPLC HSS T3(150 mm×2.1 mm,1.8μm);流动相为甲醇-0.1 mol/L乙酸铵溶液(88∶12,V/V),流速为0.2 m L/min;检测波长为210 nm;柱温为30℃;进样量为5μL。结果:齐墩果酸和熊果酸的检测质量浓度线性范围分别为10.65~1 065μg/m L(r=0.999 6)、18.8~1 880μg/m L(r=0.999 4),平均加样回收率分别为96.95%(RSD=1.24%,n=9)、98.12%(RSD=2.13%,n=9),精密度、稳定性、重复性试验的RSD均小于3%。不同药用部位的齐墩果酸和熊果酸含量的高低整体趋势为地上部位>全草>地下部位;翼首草全草中齐墩果酸和熊果酸平均总量为0.35%,地上部位中为0.56%,地下部位中为0.09%。结论:建立的方法快速、准确可靠、重复性好,适合于藏药翼首草不同药用部位中齐墩果酸和熊果酸含量的测定。翼首草地上部位中齐墩果酸和熊果酸含量较全草、地下部位高,建议使用地上部位入药。     

反相高效液相色谱法测定陆英中乌索酸和齐墩果酸含量

目的建立陆英药材中乌索酸和齐墩果酸含量的测定方法。方法选用SymmetryC18(3.9mm×150mm,5μm)色谱柱,流动相甲醇-水(88∶12),检测波长220nm,流速0.6mL/min,柱温25℃。结果乌索酸的线性范围0.098~2.35μg,r=0.9999;齐墩果酸的线性范围0.099~2.38μg,r=0.9997。乌索酸和齐墩果酸平均回收率分别为97.9%(RSD为2.11%)和98.6%(RSD为1.84%)。结论本法可同时测定乌索酸和齐墩果酸含量,具有准确、灵敏、数据可靠的优点,可用于陆英药材的质量控制。     

高效液相色谱质谱法测定齐墩果酸固体分散物的溶出度研究

目的: 建立齐墩果酸高效液相色谱质谱联用(HPLC MS)浓度测定方法,并用于溶出度实验时溶出液中齐墩果酸的测定。方法:采用高效液相色谱质谱联用法测定齐墩果酸固体分散物溶出度实验中齐墩果酸的浓度。结果: 在0. 2 ~12. 8mg·L-1的浓度范围内,齐墩果酸线性关系良好(r= 0. 999 7 ),高、中、低浓度回收率分别为98. 6 %, 99. 3 %, 102. 4 % (n=5),日内RSD低于5. 0 % (n=5),日间RSD低于10. 0 % (n=5)。结论:本方法灵敏度高、分析时间短、杂质干扰少,可用于齐墩果酸溶出度实验的研究及制剂含量的测定。     

γ-环糊精流动相添加剂法分离测定木瓜中的齐墩果酸和熊果酸

目的建立木瓜中齐墩果酸和熊果酸的反相高效液相分析方法,为木瓜的质量控制提供依据。方法色谱柱为Kromasil C18 ODS(150mm×4.6 mm,5μm);流动相为乙腈-2 mmol·L-1γ-CD水溶液(含1 mL·L-1磷酸)(60∶40);流速为1.0mL·min-1;检测波长为210nm。结果齐墩果酸和熊果酸的分离良好,分离度为3.10;齐墩果酸在0.6~3.0μg(r=0.999 9)、熊果酸在1.2~6.0μg(r=0.999 9)范围内线性关系良好;平均回收率分别为99.4%(RSD=2.0%)和99.1%(RSD=2.2%)。结论该方法简便、准确可靠,可作为木瓜的质量控制方法。     

木凤胶囊中齐墩果酸的含量

目的建立木凤胶囊中齐墩果酸的含量测定方法。方法高效液相色谱法(HPLC),流动相为甲醇-0.4%磷酸溶液(90:10);检测波长为210nm;柱温40℃。结果齐墩果酸线性范围为50.2～351.4μg.mL-1(r=0.9999),平均回收率98.32%,RSD%为1.1%(n=9)。结论方法可靠、简单可行,为控制木凤胶囊的质量提供了科学依据。     

超微粉碎技术提高齐墩果酸滴丸溶出度的实验研究

目的:研究超微粉碎技术应用于齐墩果酸滴丸生产的可行性及效果。方法:采用超微粉碎技术制备齐墩果酸超微粉滴丸并与齐墩果酸普通滴丸相比较,采用紫外分光光度法进行溶出度测定。结果:齐墩果酸浓度在0.020 74~0.072 59 mg/ml内呈良好线性关系(r=0.999 7,n=6);溶出度均一性良好;45 min时齐墩果酸滴丸的溶出度达到95.24%,远高于普通滴丸(82.36%)、胶囊剂(75.32%)和分散片(52.17%)。结论:采用超微粉碎技术制备的齐墩果酸滴丸剂各项指标均优于未处理过的,超微粉碎技术用于齐墩果酸滴丸生产可显著改善滴丸的性状及质量。     

齐墩果酸滴丸的质量标准研究

目的:建立齐墩果酸滴丸的质量标准。方法:鉴别制剂性状,检测制剂重量差异、溶散时限;采用超高效液相色谱法测定制剂中齐墩果酸的含量:色谱柱为ACQUITY UPLC BEH C_(18),流动相为乙腈-水(70∶30,V/V),流速为0.30 mL/min,检测波长为206 nm,柱温为30℃,进样量为5μL。结果:制剂鉴别特征明显,丸重差异为37.62%~46.56%,溶散时间均为24 min。齐墩果酸检测质量浓度线性范围为0.006~0.06 mg/mL(r=0.999 8);精密度、稳定性、重复性试验的RSD<2.0%;加样回收率为99.34%~100.40%(RSD=0.4%,n=6)。结论:该研究所建标准可用于齐墩果酸滴丸的质量控制。     

HPLC法测定齐墩果酸胶囊中齐墩果酸的含量

建立高效液相色谱法测定齐墩果酸胶囊的含量.采用HYPERSIL C18色谱柱;流动相:甲醇-0.1%磷酸溶液(90:10);流速:1.0mL·min-1;检测波长:210nm.齐墩果酸在1.018～10.18цg范围内线性关系良好(r=1.0000);齐墩果酸平均回收率99.6%,RSD=0.8%.该方法灵敏、准确,可用于齐墩果酸胶囊的含量测定.     

双波长薄层扫描法测定齐墩果酸片的含量

目的:建立齐墩果酸片的含量测定方法。方法:采用双波长薄层扫描法,以环己烷-丙酮-醋酸乙酯-冰醋酸(65:25:10:1)为展开剂,扫描波长λS=220nm,λR=330nm。结果:齐墩果酸在1~5μg范围内线性关系良好(r=0.999),平均回收率99.11%,RSD为1.56%。结论:该法简便快速,结果稳定,重现性好。     

高效液相色谱法测定胃炎停胶囊中齐墩果酸、熊果酸的含量

目的:建立HPLC法测定胃炎停胶囊中齐墩果酸、熊果酸的含量.方法:以SB-C18柱(4.6 mm×150 mm,5 μm)为分离柱,流动相:甲醇-水(85∶15),检测波长:220 nm.结果:齐墩果酸在0.36～1.80 μg范围内线性关系良好,r=0.9998,样品中齐墩果酸的含量为3.68%(mg/g),其回收率为:97.40%, RSD为2.10%(n=5);熊果酸在0.36～1.44 μg范围内线性关系良好,r=0.9980,样品中熊果酸的含量为6.49%(mg/g), 其回收率为101.21%,RSD为2.40%(n=5).结论:本法简便、准确、可靠.     

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.

     

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.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.