磺酰化新茯苓多糖的制备及抗肿瘤作用

利用碱提取酸沉淀法从茯苓Ｐｏｒｉａｃｏｃｏｓ（Ｓｃｈｗ）Ｗｏｌｆ中提取茯苓多糖，再以茯苓多糖为原料用Ｓｍｉｔｈ降解方法制备β（１→３）结合的葡萄糖（新茯苓多糖）．以二甲基甲酰胺──三乙胺──氯磺酸为磺化剂将新茯苓多糖中葡萄糖单位的羟基磺化，即制得能溶于水的部分磺酰化新茯苓多糖。利用离子交换柱层析和分子筛柱层析从总的部分磺酰化新茯苓多糖中精制出一种分子量为２６０００，硫酸酯基含量为２８．８％的部分磺酰化新茯苓多糖（ＳＮＰＣＰ）．通过理化性质和光谱数据鉴定ＳＮＰＣＰ为直链β（１→３）结合的葡聚糖，平均每１０个葡萄糖组成糖单位中有７个的６位羟基被磺酰化。动物实验表明其具有抗肿瘤作用。     

用核磁共振技术研究日本续断皂苷E_2的结构

从日本续断ＤｉｐｓａｃｕｓｊａｐｏｎｉｃｕｓＭｉｑ．根的乙醇提取物中得到一个新三萜皂苷（５糖苷），命名为日本续断皂苷Ｅ２（ｊａｐｏｎｄｉｐｓａｐｏｎｉｎＥ２）．用化学方法及１ＨＮＭＲ，１３ＣＮＭＲ，１Ｈ－１ＨＣＯＳＹ，一维多重接力ＣＯＳＹ和三重共振ＮＯＥ差谱等方法，鉴定其结构为３－Ｏ－〔β－Ｄ－吡喃葡萄糖（１→４）〕〔α－Ｌ－吡喃鼠李糖（１→３）〕－β－Ｄ－吡喃葡萄糖（１→３）－α－Ｌ－吡喃鼠李鼠（１→２）－α－Ｌ－吡喃阿拉伯糖－齐墩果酸     

知母中三个新的呋甾皂苷

从中药知母（ＡｎｅｍａｒｒｈｅｎａａｓｐｈｏｄｅｌｏｉｄｅｓＢｇｅ．）中分离出三种新的呋甾皂苷，初步鉴定为（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖－５β－呋甾－２０（２２）－双键－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（１），（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖基－２２－羟基－５β－呋甾－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（２），（２５Ｓ）－２６－Ｏ－β－Ｄ－葡萄糖基－２２－甲氧基－５β－呋甾－３β，２６－二醇－３－Ｏ－β－Ｄ－葡萄糖基（１→２）〔β－Ｄ－葡萄糖基（１→３）〕－β－Ｄ－葡萄糖基（１→４）－β－Ｄ－半乳糖苷（３）．分别命名为ｔｉｍｏｓａｐｏｎｉｎ－ＢⅣ，ｔｉｍｏ－ｓａｐｏｎｉｎ－ＢⅤ，ｔｉｍｏｓａｐｏｎｉｎ－ＢⅥ．     

金不换山酮成分的研究Ⅲ一个新山酮甙的结构测定

从民族药金不换（ＶｅｒａｔｒｉｌｌａｂａｉｌｌｏｎｉｉＦｒａｎｃｈ）根中分离到多种酮化合物，经化学及光谱法测定，其中之一为２，３，４，７－四甲氧基酮－１－Ｏ－β－Ｄ－木糖基（１→６）－β－Ｄ－葡萄糖甙（Ⅰ），是新的酮甙。     

香菇多糖构效关系、抗肿瘤作用机制及药代动力学研究进展

香菇多糖(lentinan, LNT)是从香菇子实体中提取纯化的最主要生物活性成分，主要为C6分支的β-(1→3)-D-吡喃葡聚糖主链结构。LNT具有显著的免疫调节及抑制肿瘤生长作用，广泛用于临床抗肿瘤辅助治疗，能有效改善肿瘤患者的生活质量。然而，由于其提取纯化工艺繁琐，构象信息和构效关系缺乏，直接抗肿瘤作用机制尚无定论，体内代谢过程不明确，极大限制了LNT的临床应用。该文主要对香菇多糖的提取方法、构效关系、抗肿瘤作用机制及药动学进行综述，以期为香菇多糖的临床合理应用提供参考。     

云南甘草皂甙A和B结构鉴定

从云南甘草中分出２个新皂甙。根据理化性质和光谱数据，鉴定这两个新皂甙为：３β－羟基齐墩果－１１，１３－二烯－２９－羧酸－３－Ｏ－β－Ｄ－吡喃葡萄糖醛酸基（１→４）β－Ｄ－吡喃葡萄糖醛酸甙和３β，２１α－二羟基齐墩果－１１，１３二烯－２９－羧酸－３－Ｏ－β－Ｄ－吡喃葡萄糖醛酸基（１→４）β－Ｄ－吡喃葡萄糖醛酸甙，分别命名为：云南甘草皂甙Ａ和Ｂ。     

香菇多糖的免疫调节作用

检测香菇多糖（ＬＮＴ）对环磷酰胺（Ｃｙ）诱导的免疫功能低下的小鼠脾细胞溶血素抗体（ＩｇＭ）生成的影响和对ＣｏｎＡ诱导小鼠脾淋巴细胞增殖反应和ＩＬ－２生成的影响。结果表明，国产ＬＮＴ的３种剂量（０．５，１，２ｍｇ·ｋｇ－１·ｄ－１×５ｄ，ｉｐ）显著促进ＩｇＭ抗体的生成，且以１ｍｇ·ｋｇ－１·ｄ－１作用最佳。ＬＮＴ（１～１２５ｍｇ·Ｌ－１）可明显促进ＣｏｎＡ诱导的脾淋巴细胞增殖反应和ＩＬ－２的生成。量效曲线呈钟罩形。提示有浓度依赖性的双向免疫调节作用。     

一种水溶黑粉菌多糖的结构和抗肿瘤活性研究

从药用黑粉菌中用２％氢氧化钠分离提取出一种具有（１→６）分支的（１→３）－β－Ｄ葡萄糖（ＢＲ－１）．多糖ＢＲ－１的纯度用凝胶过小和超离心进行了鉴定。分子量为１５万,ＢＲ－１的一级结构分别为＾１３Ｃ核磁共振法、甲基化法、高碘酸氧化法和Ｓｍｉｔｈ降角等方法进行了确定。ＢＲ－对小白鼠肉瘤Ｓ１８０的抑瘤率为９４．０％。     

新吩嗪化合物K＿3－Ye的分离和结构鉴定

自一株基因工程链霉菌Ｋ３的发酵液中分离得到一吩嗪类新化合物，经光谱数据（ＵＬ，ＩＲ，１ＨＮＭＲ，１３ＣＮＭＲ，ＤＥＰＴ）分析，确定其结构为１－吩嗪氧基乙酸甲酯，代号Ｋ３－Ｙｅ。经初步测定它有较强的抗核苷转运活性。     

香菇多糖冲剂辐射和保护急性肝损伤的实验研究

香菇多糖冲剂５．０ｇ／ｋｇ、２．５ｇ／ｋｇ给小鼠ｉｇ３ｄ，用＾６０Ｃｏ－γ射线照射造模型，并继续ｉｇ给药治疗１Ｗ。     

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.