西沙软珊瑚Lemnalia sp.倍半萜类次级代谢产物研究

目的 对采自西沙群岛的软珊瑚样品Lemnalia sp.进行倍半萜类次级代谢产物的研究。方法 利用薄层色谱、硅胶柱层析、中压制备液相色谱和高效液相色谱等现代分离手段对软珊瑚浸膏进行分离、纯化,得到单个化合物;综合运用核磁共振、质谱等现代波谱学方法,通过与文献报道的数据进行对比,对所分离化合物的结构进行鉴定。结果 从西沙软珊瑚Lemnalia sp.中分离鉴定得到10个倍半萜类化合物,分别为Lemnardosinanes D (1)、flavalin E (2)、paralemnolin R (3)、Pathylactone A (4)、(+)-13-hydroxy-aristlone (5)、Laevinone A (6)、(+)-curcudiol (7)、oplodiol (8)、6-Eudesmene-1β, 4β-diol (9)、Paralemnolide A (10)。结论 从软珊瑚Lemnalia sp.中分离得到10个已知的倍半萜类化合物,其化学结构类型分别属于nardosinane型、nornardosinane型、aristolane型、neolemnane型、bisabolane型、eudesmane型和bisnorsesquiterpene型,其中化合物4、5、7~10是首次在该属软珊瑚中发现的倍半萜。     

西沙软珊瑚Paralemnalia sp.倍半萜类次级代谢产物研究

目的 对采自西沙群岛的软珊瑚样品Paralemnalia sp.进行倍半萜类化学成分的研究。方法 利用硅胶柱层析、薄层色谱、中压制备型液相色谱和高效液相色谱等现代分离手段对软珊瑚样品浸膏进行分离、纯化,得到单一化合物;综合运用核磁共振波谱、质谱等现代波谱学方法,通过与已知文献报道的数据进行对比,对分离得到的化合物结构进行鉴定。结果 从西沙软珊瑚Paralemnalia sp.中分离鉴定得到10个倍半萜类化合物,分别为4-Acetoxy-2,8-neolemnadien-S-one(1)、Sinulatumolin E(2)、paralemnolin E(3)、paralemnolin G(4)、paralemnolin B(5)、12-acetoxy-1(10)-aristolene(6)、1(10)-Aristolen-2-one(7)、Aristolan-1,9-diene(8)、9α-hydroxy-calarene(9)、13-hydroxy-1(10)-aristolen-2-one(10)。结论 从西沙软珊瑚Paralemnalia sp.中分离得到10个已知的倍半萜类化合物,其化学结构类型分别属于neolemnane型、nornardosinane型和nardosinane型,其中,化合物1,6~10为首次在该属软珊瑚中被发现。     

肿节风倍半萜类化学成分研究

为了研究肿节风全草中倍半萜类化学成分,利用硅胶柱色谱、凝胶柱色谱、ODS柱色谱及制备液相色谱等分离技术从肿节风70%乙醇提取物的正丁醇和乙酸乙酯萃取部分分离得到4个倍半萜内酯类成分,根据化合物的光谱数据分别鉴定为4α-hydroxy-5αH-lindan-8(9)-en-8,12-olide(1)、chloranthalactone E(2)、8β,9α-dihydroxylindan-(5),7(1)-ieb-8α,12-olide(3)和chloranoside A(4)。其中化合物1为新化合物。     

西沙群岛软珊瑚Lemnalia sp.倍半萜类次级代谢产物研究

目的 对西沙群岛软珊瑚样品Lemnalia sp.进行萜类次级代谢产物的化学结构研究。方法 利用薄层色谱、硅胶柱层析、高效液相色谱和中压制备液相色谱等分离手段对软珊瑚提取物中的化合物进行分离、纯化;运用核磁共振、质谱等现代波谱学方法,通过与报道的数据进行对比,对化合物的化学结构进行了鉴定。结果 从西沙群岛软珊瑚Lemnalia sp.中分离鉴定10个倍半萜类化合物,分别为4-acetoxy-2,8-neolemnadien-5-one（1）、paralemnolin E（2）、paralemnolin H（3）、paralemnolin L（4）、paralemnolin J（5）、2-deoxy-7-O-methyllemnacarnol（6）、parathyrsoidin D（7）、(1aS,4S,4aS,5S,8aR)-5-acetyl-4,4a-dimethyloctahydro-6H-naphtho[1,8a-b]oxiren-6-one（8）、paralemnolin K（9）和paralemnolin P（10）。结论 从软珊瑚Lemnalia sp.中分离得到10个已知的倍半萜类化合物,化学结构类型分别属于neolemnane型、nardosinane型和nornardosinane型,其中,化合物2-10为首次从Lemnalia属软珊瑚中得到。     

南海小月柳珊瑚中倍半萜类化学成分研究(英文)

对南海小月柳珊瑚Menellasp.的化学成分进行研究。应用反复硅胶柱层析、Sephadex LH-20柱色谱和制备薄层等多种色谱方法进行分离和纯化。从中分离得到3个subergorane倍半萜和1个suberosane倍半萜化合物,利用波谱分析技术和文献比对等方法确定化合物的结构,分别为柳珊瑚酸(1),柳珊瑚酸甲酯(2),2β-羟基柳珊瑚酸甲酯(3)和suberosenol A(4)。以上化合物均为首次从小月柳珊瑚属(Menella)中分离得到。     

温郁金中的新桉叶烷型倍半萜內酯

为了研究温郁金(Curcuma wenyujin Y.H. Chen et C. Ling)根茎中的倍半萜类成分，采用大孔树脂和反复硅胶柱色谱对温郁金干燥根茎的50%乙醇提取物进行分离纯化，得到8个倍半萜类化合物1～8；其化学结构通过多种波谱方法分别鉴定为温郁金内酯A(wenyujinlactone A，1)、neolitamone A (2)、zedoarondiol (3)、isozedoarondiol (4)、aerugidiol (5)、莪术醇(curcumol，6)、莪二酮(curdione，7)和(1R,10R)-epoxy-(-)-1,10-dihydrocurdine (8)。化合物1为新的桉叶烷型倍半萜内酯，化合物2～5为首次从该植物中分离得到。     

毛莲蒿中倍半萜类化学成分研究

研究蒿属植物毛莲蒿地上部分倍半萜类化学成分, 通过硅胶柱色谱、反相硅胶柱色谱、制备高效液相色谱等色谱方法分离得到12个倍半萜类成分, 经多种波谱方法鉴定其结构, 分别为negunfurol (1), schensianol A (2), artemine (3), eudesm-4(14)-en-12-oic acid, erivanin (4), 1,5-diepi-artemin (5), acetylartemin (6), naphtho[1,2-b]furan-2(3H)-one,6-(acetyloxy)- decahydro-9a-hydroxy-3,5a-dimethyl-9-methylene-(3S,3aS,5aS,6S,9aS,9bS) (7), naphtho[1,2-b]furan-2(3H)-one,6-(acetyloxy)- 3a,4,5,5a,6,7,8,9b-octahydro-8-hydroxy-3,5a,9-trimethyl-(3S,3aS,5aR,6S,8S,9bS) (8), isoerivanin (9), barrelierin (10), (11S)-1- oxoeudesm-4(14)-eno-13,6α-lactone (11), 1-epi-dehydroisoeranin (12)。其中化合物1和2为首次从蒿属植物中分离得到, 其它化合物均为首次从毛莲蒿中分离得到。     

乌药叶中黄酮类成分研究(2)

目的研究乌药叶的抗菌、抗炎有效成分。方法采用多种色谱学 ,化学及波谱学等方法进行分离与结构鉴定。结果在以前研究的基础上 ,又从乌药叶中分离得到 4个黄酮类化合物和 1个倍半萜类化合物 :乌药醇 (5 ) ,4个黄酮类化合物分别被鉴定为nubigenol(1 ) ,山奈酚 3 O (6″ 反式 对 肉桂酰基 ) β D 吡喃葡萄糖苷 (2 ) ,香叶木素 7 O β D 葡萄糖苷 (3 )和芦丁 (4 )。 结论这 4个黄酮类化合物均为属内首次分离得到     

涠洲岛沐浴角骨海绵Spongia officinalis的化学成分研究

目的 研究采自广西涠洲岛的沐浴角骨海绵Spongia officinalis的化学成分。方法 利用硅胶柱色谱、Sephadex LH-20凝胶柱色谱、半制备HPLC等色谱技术对其化学成分进行分离、纯化;通过NMR、MS方法,结合与文献报道的数据的比对,对化合物的结构进行鉴定。结果 从该海绵的乙醚相浸膏中分离得到了二倍半萜fasciculation（4）及3个C21呋喃萜类化合物 (–)-untenospongin B（1）,kurospongin（2）和C21 fasciculatin acid（3）。结论 本研究是对涠洲岛的沐浴角骨海绵Spongia officinalis化学成分的首次报道,4个化合物均为首次从涠洲岛的该种海绵中分离得到,其中化合物3是新天然产物。     

西沙短指软珊瑚Sinularia multiflora化学成分研究△

目的 研究中国南海西沙群岛软珊瑚Sinularia multiflora的化学成分。方法 利用薄层色谱、硅胶柱层析、Sephadex LH-20柱层析、MPLC、HPLC等色谱方法对化学成分进行分离纯化;运用NMR、MS等波谱方法,并结合文献理化数据比对,鉴定化合物的结构。结果 从西沙短指软珊瑚Sinularia multiflora的甲醇-二氯甲烷粗提取物中分离得到7个降碳二萜类化合物：(5R)-norcembrene (1),(5S)-norcembrene (2),norcembrene C (3),sinuleptolide (4),scabrolide C (5),norcembrene E (6),ineleganolide (7),以及1个已知愈创木烷型倍半萜：3β-methoxy-guaia-2β-ol-10(14)-ene (8)。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

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.