中国南海蜂海绵Haliclona cymae formis的化学成分研究

目的研究中国南海蜂海绵属Haliclona cymaeformis的化学成分。方法运用正相硅胶、反相硅胶(ODS)和凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化;通过理化性质和波谱数据,结合文献对照,鉴定化合物的结构。结果从海绵H.cymaeformis的乙醇提取物中共分离鉴定了11个单体化合物:24-亚甲基胆甾醇(1),5α,8β-epidioxy-cholesta-6-en-3-ol(2),cholesta-7-en-3β,5α,6β,9α-tetraol(3),胆甾醇(4),3-吲哚甲酸(5),尿嘧啶(6),胸腺嘧啶(7),尿嘧啶核苷(8),胸腺嘧啶核苷(9),尿嘧啶脱氧核苷(10)和胸腺嘧啶脱氧核苷(11)。结论化合物1~11均为首次从该海绵中分离得到。细胞毒活性测试结果表明,化合物3对慢性髓原白血病细胞(K562)和人肝癌细胞(SMMC-7721)的增殖显示了较强的生长抑制活性。     

中国南海海绵Iotrochota sp.的化学成分研究D*

目的 研究中国南海海绵Iotrochota sp.的化学成分。方法 应用正、反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱、半制备反相高效液相色谱(RP-HPLC)等多种色谱手段,对海绵Iotrochota sp.的二氯甲烷提取物进行分离纯化,从中得到6个单体化合物,运用现代波谱技术结合文献报道对其进行结构鉴定,采用MTT法对分离得到的6个化合物进行人高转移肝癌细胞(LM3)和人肝癌细胞(HepG2)的体外抗肿瘤活性测试。结果 分离得到6个化合物,包括4个吲哚生物碱类化合物(1-4)及2个酚类化合物(5、6),分别鉴定为：1H-indole-3-carbaldehyde(1)、5-bromo-1H-indole-3-carbaldehyde(2)、1H-indole-3-hydroxyacetyl(3)、5-bromo-3-(hydroxylacetyl)-indole(4)、4-hydroxy-benzeneethanol(5)、3-hydroxy- benzeneethanol(6)。这些化合物均为首次从海绵Iotrochota sp.中分离得到,化合物2和4为C-5溴代吲哚生物碱,本文首次对其NMR数据进行了报道。体外抗肿瘤活性测试显示,化合物3对LM3及HepG2细胞株显示不同程度的抑制活性,IC₅₀值分别为29.3及46.3 μM;其他化合物不显示抑制作用(IC₅₀>50 μM)。     

西沙海绵Agelas aff. Nemoechinata化学成分研究△

目的 研究中国西沙海绵Agelas aff. Nemoechinata 二氯甲烷/甲醇部分的化学成分。方法 运用薄层色谱、硅胶柱色谱、Sephadex LH-20凝胶柱色谱、MPLC、HPLC等分离方法对该海绵化学成分进行分离纯化;利用核磁共振、质谱等结构鉴定技术,并结合文献,鉴定化合物的结构。结果 从海绵甲醇粗提物的二氯甲烷/甲醇部分分离鉴定了7个化合物：agelasine B (1)、2-oxo-agelasine B (2)、2’-oxo-agelasidine C (3)、2-甲酸吡咯负离子 (4)、2-甲酰胺吡咯 (5)、9-甲基腺嘌呤 (6)和尿嘧啶 (7)。结论 化合物1、2、3、4和6均为首次从该种分离得到。     

中国南海群海绵Agelas mauritiana的化学成分研究

目的 对采自南中国海海域的群海绵(Agelas mauritiana)的化学成分进行研究。方法采用硅胶色谱柱、Sephadex LH-20凝胶色谱柱、高效液相色谱等色谱方法,对Agelas mauritiana正丁醇萃取物进行分离纯化;应用现代波谱技术对化合物进行化学结构鉴定;用MTT法对化合物进行体外人肺癌细胞株A549细胞生长抑制活性测试。结果 共分离得到8个化合物,分别鉴定为:agelasine A(1)、agelasine B(2)、epi-agelasine C(3)、(-)agelasine D(4)、agelasine E(5)、agelasine F(6)、(-)ageloxime D(7)、aurantiamide acetate(8)。体外活性筛选中,这些化合物对A549显示出不同程度的生长抑制活性,化合物1~3的活性与阳性对照阿霉素相近。结论 化合物1、2、4、5、6、8为首次从该种海绵中分离得到。首次选用A549对化合物1~7的活性进行评价,化合物2、3的显著生长抑制活性为进一步深入研究提供了依据。     

中国南海海绵Cinachyrella sp.的化学成分研究

目的 研究中国南海海绵Cinachyrella sp.的化学成分。方法 采用硅胶柱色谱、Sephadex LH-20凝胶色谱及半制备型高效液相色谱对Cinachyrella sp.海绵中的化学成分进行分离和纯化,通过核磁共振、质谱、紫外等解析化合物结构并结合文献中的数据对比鉴定所得化合物,并且对分离得到的化合物进行抗菌活性测试。结果 从Cinachyrella sp.海绵中分离鉴定了15个化合物：喹啉-4-甲醛肟(1)、环(L-脯氨酸-L-缬氨酸)二肽(2)、环(L-脯氨酸-L-亮氨酸)二肽 (3)、环(L-脯氨酸-L-异亮氨酸)二肽(4)、苯甲酸(5)、苯乙酸(6)、苯乙酰胺(7)、胸腺嘧啶(8)、尿嘧啶 (9)、腺嘌呤核苷(10)、胸腺嘧啶脱氧核苷(11)、尿嘧啶苷(12)、3-吲哚甲醛(13)、吲哚乙酰胺(14)、吲哚-3-甲酸(15)。结论 化合物1～4均为首次从该属海绵中分离得到;抗菌活性测试中化合物2～4对6种细菌MIC值均大于64 μg/mL,提示其抑菌活性较弱。     

一种西沙掘海绵Dysidea sp.的化学成分研究

目的 对西沙掘海绵Dysidea sp.进行化学成分研究;方法 运用正相硅胶柱色谱、反相ODS柱色谱、凝胶Sephadex LH-20柱色谱以及高效液相色谱(HPLC)等多种分离手段对西沙掘海绵Dysidea sp.化学成分进行分离纯化;并通过理化性质、波谱学数据等结构信息鉴定其化合物的结构。结果发现：从西沙掘海绵Dysidea sp.中分离鉴定了8个化合物,分别为dictyoceratin C（1）、dactyloquinone B（2）、aminoquinone（3）、dictyoceratin A（4）、dactyloquinone D（5）、dactyloquinone E（6）、(1R*,2E,4R*,7E,10S*,11S*,12R*)-10,18-diacetoxydolabella-2,7-dien-6-one（7）和?,?-unsaturated ester（8）,结论 化合物1?6和8均为首次从该属海绵中分离得到。     

养殖喘水苔海绵Tedania anhelans化学成分及其生物活性研究

目的研究养殖喘水苔海绵Tedania anhelans化学成分及其生物活性,为药源海绵规模化养殖和开发提供依据。方法综合利用薄层色谱、硅胶色谱、ODS C18色谱、Sephadex LH-20凝胶柱色谱、半制备高效液相色谱(HPLC)等方法对化学成分进行了分离;通过质量光谱测定(MS)、核磁共振(NMR)等方法并结合相关文献,对化合物结构进行鉴定。结果从养殖喘水苔海绵Tedania anhelans中分离得到13个化合物,分别为胆固醇(1)、3β-羟基-24-亚甲基胆甾-5-烯-7-酮(2)、胆甾-5-烯-3β,7α-二醇(3)、胆甾-5-烯-3β,7β-二醇(4)、3β-羟基胆甾-5-烯-7-酮(5)、胸苷(6)、去甲基胸苷(7)、环(脯氨酸-缬氨酸)二肽(8)、piperazirum(9)、(E)-4-(1H-indol-3-yl)but-3-en-2-one(10)、3-吲哚乙酸甲酯(11)、3-吲哚甲醛(12)、毛脉五味子醇(13)。结论 13个化合物均为首次从该种海绵中分离得到,化合物8在50μmol·L-1浓度水平对HSV-2病毒抑制率为60.7%。     

中国南海高领类尖柳珊瑚Muriceides collaris化学成分研究

目的研究中国南海高领类尖柳珊瑚Muriceides collaris的化学成分。方法利用硅胶柱色谱、Seph-adex LH-20柱色谱、HPLC等手段对化合物进行分离纯化;通过理化性质和波谱分析方法,结合文献对照,鉴定化合物的结构。结果从高领类尖柳珊瑚甲醇提取物中共分离得到了9个单体化合物:胆甾醇(1),鲨肝醇(2),苯甲酸(3),尿嘧啶(4),胸腺嘧啶(5),2’-脱氧尿嘧啶核苷(6),2’-脱氧胸腺嘧啶核苷(7),胸腺嘧啶核苷(8)和2’-脱氧腺嘌呤核苷(9)。结论化合物1～9均为首次从该种柳珊瑚中分离得到。     

西沙海绵Dysidea granulosa 化学成分研究

目的 研究中国西沙群岛海绵Dysidea granulosa的化学成分。 方法 利用薄层色谱、硅胶色谱、Sephadex LH-20色谱、MPLC、半制备HPLC等方法对化学成分进行分离纯化;通过NMR、MS等方法,并结合文献,鉴定化合物的结构。结果 从西沙海绵Dysidea granulosa的甲醇粗提取物中,分离得到6个化合物： Honulactone A (1), Honulactone B(2), Honulactone E (3), Honulactone F (4), 2-(2’,4’-Dibromophenoxy)-4,6-dibromophenol (5), 3,5-Dibromo-6-chloro-2-(2,4- dibromophenoxy)phenol (6)。结论 化合物1、2、3、4均为首次从该种海绵中分离得到。     

养殖叶片山海绵 (Mycale phyllophila) 次生代谢产物的研究△

目的 研究养殖叶片山海绵Mycale phyllophila次生代谢产物,为药源海绵规模化养殖和开发提供依据。方法 综合利用硅胶柱色谱、Sephadex LH-20凝胶柱色谱、反相ODS柱色谱、半制备液相色谱等分离技术,对化学成分进行分离;结合NMR、MS等光谱方法和文献数据,鉴定化合物的结构。结果 从叶片山海绵的低极性萃取物中,分离鉴定了11个单体化合物：3-吲哚甲醛 (1)、(1H-indol-3-yl) oxoacetamide (2)、3-hydroxyacetyl-indole (3)、3-(2-(1H-indol-3-yl)-2-oxoethyl)-5,6-dihydropyridin-2(1H)-one (4)、胆固醇(5)、麦角甾-5, 24(28)-二烯-3β-醇(6)、胆甾-5, 22-二烯-3β-醇(7)、花生酸 (8)、1-棕榈酸甘油酯(9)、正十六烷基甘油醚 (10)和对羟基苯甲醛 (11)。结论 所有化合物均为首次从叶片山海绵M .phyllophila中获得。     

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.