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。     

辽宁海绵Aplysinopsis sp.的化学成分研究

从中国南海海域采集的海绵Aplysinopsis sp.中分离得到5个化合物。利用~1H-NMR,~(13)C-NMR,MS等波谱技术确定了其结构,分别为:(E)-3′-deimino-3′-oxoaplysinopsin(Ⅰ),(Z)-3′-deimino-3′-oxoaplysinopsin(Ⅱ),3-(2-羰基-丙基)-3-羟基-吲哚啉-2-酮(Ⅲ),3-吲哚甲醛(Ⅳ),5α,6α-环氧豆甾-7-烯-3β-醇(Ⅴ)。化合物Ⅲ、Ⅴ为首次从海绵Aplysinopsis sp,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%。     

南海棘体海绵Acanthella cavernosa中的化学成分分析

目的 对中国南海棘体海绵(Acanthella cavernosa)的次生代谢产物进行研究。方法 运用硅胶柱色谱、凝胶柱色谱、高效液相色谱等分离手段对棘体海绵的丙酮提取物进行分离纯化,根据现代波谱技术结合文献报道进行结构鉴定。结果 共分离得到9个化合物,分别鉴定为kalihinol E(1)、kalihinol A(2)、10-epi-kalihinol X(3)、10-epi-kalihinol I(4)、1H-indole-3-carboxylic acid methyl ester(5)、1H-indole-3-carboxylic acid(6)、3-buten-2-one,4-(2,3,6-trimethylphenyl)-(3E)(7)、aristolone(8)、5α,8α-epidioxy-(22E,24R)-erost-6,22-dien-3β-ol(9)。结论 化合物5~8首次从Acanthella属海绵中分离得到。     

西沙海绵Agelas aff .nemoechinata化学成分研究△

目的 研究西沙海绵Agelas aff .nemoechinata的化学成分。方法 利用Sephadex LH-20凝胶色谱、硅胶色谱、ODS色谱、HPLC等手段对化学成分进行了分离纯化;通过理化性质,波谱分析方法结合文献对照,鉴定化合物的结构。结果 从南海海绵甲醇溶剂提取物中,分离鉴定了8个单体化合物：尿嘧啶(1)、胸腺嘧啶(2)、1-H-吡啶酮(3)、胸腺嘧啶-2’-脱氧核苷(4)、2-甲酰胺吡咯(5)、3-醛基吲哚(6)、6-羟基-4,4,7a-三甲基-5,6,7,7a-四氢苯并呋喃-2(2H)酮(7)、5-氨基戊酸(8)。结论 化合物1~8均为首次从该种海绵中分离得到。化合物7 在50 μg/mL_-1浓度水平,对K562白血病细胞株、P388白血病细胞株和HeLa肿瘤细胞株的抑制率分别是38.29%、23.23%和95.57%。     

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。     

肝硬化合并门静脉海绵样变性的外科治疗(附18例分析)

目的探讨不同手术方法治疗肝硬化合并门静脉海绵样变性(CTPV)的疗效。方法18例肝硬化合并CTPV患者,行经典原位肝移植7例,其中包括肝硬化合并肝癌3例;脾切除、脾-肾静脉分流加贲门周围血管离断流术6例;脾切除加食管胃底静脉断流术(食管下端切断吻合)5例。结果行经典原位肝移植7例患者,随访0.5~3年全部存活(1例因肝癌转移仍在治疗中),脾亢及食管胃底静脉曲张消失,无上消化道出血发生,彩色多普勒检查示CTPV完全消失。行脾切除、脾-肾静脉分流加贲门周围血管离断术6例患者,术后随访3~5年,l例死于肝功能衰竭,仍存活5例中1例反复发生肝性脑病、1例术后2年出现脾-肾静脉分流处血栓并再发上消化道出血,彩色多普勒检查示CTPV减轻。行脾切除加食管胃底静脉断流术(食管下端切断吻合)5例患者,术后随访3~6年,1例死于肝功能衰竭,1例死于上消化道大出血,仍存活3例中均有反复上消化道出血发生,彩色多普勒检查示CTPV加重或无改变。结论肝硬化合并CTPV的外科治疗,以原位肝移植为首选,脾切除、脾-肾静脉分流加断流术优于脾切除加断流术。     

吸收性甲硝唑明胶海绵治疗牙周病临床体会

我科自1998~2000年用吸收性甲硝唑明胶海绵置入牙周袋内治疗各型牙周病65例，临床疗效显著，现报道如下。 1 对象和方法 门诊患者共65例，其中男35例(急性牙周炎15例，慢性牙周炎18例，急性牙周脓肿2例)，女30例(急性牙周炎9例，慢性牙周炎16例，急性牙周脓肿2例，急性冠周炎3例)。年龄31~65岁。取市售甲硝唑1g，加入蒸馏水20ml，其浓度为0.05g/ml。将剪成1mm宽条状明胶海绵浸泡其中，室温下干燥密封备用。治疗时先平整牙面，用生理盐水冲洗后擦干，夹取药条置入牙周袋内。 2 疗效判定 放置一次药条后48~96h内牙周无溢脓，牙龈无…     

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Haliclona baeri的化学成分研究

目的 对采自中国南海海域海绵Haliclona baeri 95 %乙醇提取物的乙酸乙酯部位的化学成分进行研究。方法 运用薄层色谱、正相Silica gel柱色谱、SephadexLH-20柱色谱以及HPLC等色谱分离手段;通过NMR、MS等波谱学方法,并结合文献报道,鉴定化合物的结构。结果 从海绵H. baeri中分离并鉴定了5个吲哚生物碱,分别为：(1H-indol-3-yl) oxoacetamide (1)、1H-indole-3-acetamide (2)、1H-indole-3-ethylethanoate (3)、1H-indole-3-carboxylic acid ethyl ester (4)和1H-indole-3-carboxylic acid (5)。结论 化合物1-4为首次从该属海绵中分离得到。对化合物1进行生物活性测试,该化合物没有表现出明显的细胞毒、抗核因子κB、抗菌、抗病毒和抗污损活性。     

Effects of freezing on human skin permeability

The percutaneous absorption of water was measured in-vitro at 30 degrees C for pale caucasian abdominal skin which had been stored at -20 degrees C for up to 466 days and compared with fresh skin. Prolonged freezing of the skin did not affect the absorption of water which had a mean permeability coefficient of 1.71 +/- 0.62 X 10(-3) cm h-1 (180 diffusion experiments with 39 skin specimens). No significant difference was found between the absorption of water through human skin which was fresh or had been frozen. The mean permeability coefficient for skin which had not been frozen was 1.30 +/- 0.55 X 10(-3) cm h-1 for 6 skin specimens.     

Pseudopolymorphism and phase stability in four solid forms of (6R,7R)-7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-(Z)-2-methoxy- iminoacetamid]-3- [(4-carbamoyl-1-quinuclidinio)methyl]-8-oxo-5-thia-1-azabicyclo - [4,2,0]oct-2-ene-2-carboxylate (E1040)

(6R,7R)-7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-(Z)-2-methoxy- iminoacetamid]-3- [(4-carbamoyl-1-quinuclidinio)methyl]-8-oxo-5-thia-1-azabicyclo [4,2,0]oct-2-ene-2-carboxylate (1; E1040) was isolated as alpha-(decahydrate), beta-(pentahydrate), and gamma-form (anhydrate) crystals and the X-ray amorphous form. The relationship between the pseudopolymorphic crystal forms of this compound and water content was studied by X-ray diffractometry, coulometric moisture analysis, thermal analysis, and hygroscopic and vacuum-freeze-drying experiments. The phase transition of crystalline 1 clearly indicated the effect of water content on dehydration. During dehydration, hydrated alpha-form (decahydrate) crystals and beta-form (pentahydrate) crystals became anhydrate gamma-form crystals, with the diffraction angle shifting toward shorter spacing accompanied by line broadening. These results indicate conversion of hydrate 1 crystals to the anhydrous form and contraction of the crystal lattice. It was estimated that the decahydrate (alpha-form) crystals contain 8 mol/mol crystal water and 2 mol/mol adhesion water, and that the pentahydrate (beta-form) crystals contain 4 mol/mol crystal water and 1 mol/mol adhesion water. These estimates were made by comparing the data from equilibrium hydration experiments and vacuum-freeze-drying experiments. It thus follows that gamma-form crystals are anhydrate and the X-ray amorphous form exists in either the hydrous or anhydrous form.     

黄芩苷在大鼠胃、离体小肠的吸收动力学研究

通过高效液相色谱法研究了黄芩苷在大鼠胃、离体小肠的吸收情况,采用ＮＵＣＬｅｏｓｉｌ Ｃ１８（５ μｍ）４ ｍ ｍ ×２５０ ｍ ｍ 色谱柱,以甲醇 水 乙酸（６０∶３９∶１） 为流动相,检测波长２７６ ｎｍ ,柱温：室温,本实验对大鼠胃和离体小肠在不同ｐＨ 条件下的吸收动力学进行了研究,实验结果：大鼠胃的吸收率与黄芩苷的油／ 水分配系数之间相关方程为：吸收率＝ ０ ．０３０ ５７１ ｇ（ 油／ 水分配系数） － ２ ．１２６（ｒ＝ ０－９７３１） ;大鼠离体小肠的吸收率与黄芩苷的油／ 水分配系数之间相关方程为：吸收率＝０－０８４ １ ×１ ｇ（ 油／ 水分配系数） － ３－２５４（ｒ＝ ０．９９６ ２） ．     

The crystal structure of acemetacin monohydrate (C21H18NO6Cl−H2O), A non-steroidal antiinflammatory agent

The molecular structure of acemetacin, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid carboxymethyl ester, was determined by single crystal X-ray diffraction analysis. The compound was recrystallized from a mixture of acetone and water in triclinic, space group P1, with a=7.796(1), b=10.245(2), c=13.542(3) Å, α=97.35(1), β=96.34(1), ψ=107.06(1)°, and Z=2. The calculated density is 1.422; the observed value is 1.42 g/cm³. The structure was solved by the direct method and refined by full matrix least-squares procedure to the final R value of 0.037 for 2960 independent reflections. There are water molecules, which are thought to be co-crystallized during the evaporation procedure, with the ratio of one water per compound molecule in the crystal. The conformation of the compound is found to be very similar to that of indomethacin. The molecules are stabilized by three O?H…O type intermolecular hydrogen bonds between the oxygen of water molecule and those of the compound.     

Assessing the risks on human health associated with inorganic arsenic intake from groundwater-cultured milkfish in southwestern Taiwan.

The risk of consuming groundwater-cultured milkfish (Chanos chanos) was assessed. Samples of water and milkfish from groundwater-cultured ponds in southwestern Taiwan were analyzed. One third of the 12 sampled ponds had arsenic concentrations in the water higher than 50 microg/L, which is the maximum allowed concentration for arsenic in aquacultural water in Taiwan. Of the total amount of arsenic in water, the percentage of inorganic arsenic was 67.5+/-8.8%. The inorganic arsenic level in milkfish was 44.1+/-10.2%. The bioconcentration factors (BCFs) of milkfish for total arsenic and inorganic arsenic were 11.55+/-4.42 and 6.8+/-2.64, respectively. The target cancer risk (TR) for intake of the milkfish from those ponds was higher than the safe standard 1 x 10(-6), while in 8 of the ponds the TR values were higher than 1 x 10(-4). Among the 12 ponds, 7 of those had the target hazard quotient (THQ) for intake of the milkfish higher than the safe standard 1. The actual consumption (IRF) of milkfish from most of those ponds were higher than the calculated acceptable consumption (RBIRF), based on TR = 1 x 10(-6)-1 x 10(-4). Only three sampled ponds (Putai 2, Peimen 2 and Peimen 3) did not show differences between the IRF and the RBIRF. Based on the standard TR = 1 x 10(-6), both the risk-based concentration for inorganic arsenic in milkfish (RBC(f)) and the risk-based concentration for inorganic arsenic in pond water (RBC(w)) were lower than the levels of inorganic arsenic in reared milkfish (C(b)) and the concentration of inorganic arsenic in pond water (C(w)), respectively. When the calculation was based on TR = 1 x 10(-4), only one sampled pond (Putai 3) had a RBC(f) value higher than C(b). The inhabitants might be exposed to arsenic pollution with carcinogenic and non-carcinogenic risks.     

The effect of water hardness on the toxicity of uranium to a tropical freshwater alga Chlorella sp

Uranium (U) derived from mining activities is of potential ecotoxicological concern to freshwater biota in tropical northern Australia. Few data are available on the effects of water hardness (Ca and/or Mg), which is elevated in U mine wastewaters, on the toxicity and bioavailability of U to freshwater biota, particularly algae. This study determined the effect of water hardness (8, 40, 100 and 400 mg CaCO(3) x l(-1), added as calcium (Ca) and magnesium (Mg) sulphate) on the toxicity (72 h growth rate inhibition) of U to the unicellular green alga, Chlorella sp., in synthetic freshwater, at constant pH (7.0) and alkalinity (8 mg CaCO(3) x l(-1)), similar in chemical composition to sandy coastal streams in tropical northern Australia. A 50-fold increase in water hardness resulted in a 5-fold decrease (P0.05) differences in the predicted speciation (% distribution) of U amongst the four water hardness levels. The reduction in U toxicity with increasing water hardness was most likely due to competition between U and Ca and/or Mg for binding sites on the algal cell surface. The minimum detectable effect concentrations of U were approximately 3 and 24 times higher (at 8 and 400 mg CaCO(3)x l(-1) hardness, respectively) than the national interim U guideline value (0.5 micro g x l(-1)) for protecting aquatic ecosystems. Overall, the results reinforce the need for a more flexible U guideline based on a hardness-dependent algorithm, which may allow environmental managers to relax the national guideline for U on a site-specific basis.     

Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite

Adenosine A1 receptor wild-type (+/+) and knockout (-/-) mice were used to elucidate the role of adenosine A1 receptors in caffeine self-administration in a two-bottle choice test and in the effect of caffeine on total fluid intake and plasma renin concentration. With access to water only, adenosine A1 receptor -/- mice showed greater basal fluid intake and greater plasma renin concentration than +/+ mice. Free access to both water and a caffeinated solution (30 mg/100 ml) for 14 days increased total fluid intake only in adenosine A1 receptor +/+ mice (by 23+/-3%), and both total fluid intake and plasma renin concentration were no longer different between genotypes. Mean intake of water and caffeinated solution was not different between adenosine A1 receptor +/+ and -/- mice. These data reveal that adenosine A1 receptors do not contribute to caffeine consumption, but determine the effects of caffeine on fluid intake and plasma renin concentration.     

Estrogenicity of butylparaben in rainbow trout Oncorhynchus mykiss exposed via food and water

The estrogenic effect of butylparaben was investigated in a rainbow trout Oncorhynchus mykiss test system. Butylparaben was administered orally to sexually immature rainbow trout every second day for up to 10 days in doses between 4 and 74 mgkg(-1)2d(-1) and in the water at 35 and 201 microgl(-1) for 12 days. Plasma vitellogenin was measured before and during the exposures and the concentrations of butylparaben in liver and muscle were determined at the end of experiments. Increases in average plasma vitellogenin levels were seen at oral exposure to 9 mg butylparaben kg(-1)2d(-1). The ED50 values for increase in vitellogenin synthesis were 46, 29 and 10.5 mg butylparaben kg(-1)2d(-1), respectively, at day 3, 6 and 12. Exposure to 201 microg butylparaben l(-1) increased vitellogenin synthesis, but exposure to 35 microgl(-1) did not. Butylparaben showed little tendency to bioaccumulation in rainbow trout; less than 1 per thousand of the total amount of butylparaben administered orally at 51 mgkg(-1)2d(-1) over the 12 days experimental period was retained in liver at the end of the experiment. After 12 days exposure to 35 and 201 microg butylparaben l(-1), plasma concentrations were 9 and 183 microgl(-1), respectively, and for the fish exposed to 201 microgl(-1) there was a positive correlation between concentrations of vitellogenin and butylparaben in the plasma. On the assumption that butylparaben removed from the water phase during water exposure were taken up into the fish, butylparaben uptake rates in the fish exposed to 35 and 201 microg butylparaben l(-1) were 13 and 78 mgkg(-1)day(-1), respectively.     

Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice

AIMS: To determine whether the pharmacokinetics of cisapride and its interaction with grapefruit juice are stereoselective. METHODS: The study was a randomized, two-phase cross over design with a washout period of 2 weeks. Ten healthy volunteers were pretreated with either water or 200 ml double strength grapefruit juice three times a day for 2 days. On the 3rd each subject ingested a single 10 mg dose of rac-cisapride tablet. Double strength grapefruit juice (200 ml) or water was administered during cisapride dosing and 0.5 and 1.5 h thereafter. Blood samples were collected before and for 32 h after cisapride administration. Plasma concentrations of cisapride enantiomers were measured by a chiral h.p.l.c. method. A standard 12-lead ECG was recorded before cisapride administration (baseline) and 2, 5, 8, and 12 h later. RESULTS: This study showed that cisapride pharmacokinetics are stereoselective. In control (water treated) subjects, the mean Cmax (30 +/- 13.6 ng ml-1; P = 0.0008) and AUC(0, infinity) (201 +/- 161 ng ml-1 h; P = 0.029) of (-)-cisapride were significantly higher than the Cmax (10.5 +/- 3.4 ng ml-1) and AUC(0, infinity) (70 +/- 51.5 ng ml-1 h) of (+)-cisapride. There was no marked difference in elimination half-life between (-)-cisapride (4.7 +/- 2.7 h) and (+)-cisapride (4.8 +/- 3 h). Compared with the water treated group, grapefruit juice significantly increased the mean Cmax of (-)-cisapride from 30 +/- 13.6-55.5 +/- 18 ng ml-1 (95% CI on mean difference, -33, -17; P = 0.00005) and of (+)-cisapride from 10.5 +/- 3.4 to 18.4 +/- 6.2 ng ml-1 (95% CI on mean difference, -11.8, -3.9, P = 0.00015). The mean AUC(0, infinity) of (-)-cisapride was increased from 201 +/- 161 to 521.6 +/- 303 ng ml-1 h (95% CI on mean difference, -439, -202; P = 0.0002) and that of (+)-cisapride from 70 +/- 51.5 to 170 +/- 91 ng ml-1 h (95% CI on mean difference, -143, -53; P = 0.0005). The tmax was also significantly increased for both enantiomers (from 1.35 to 2.8 h for (-)-cisapride and from 1.75 to 2.9 h for (+)-cisapride in the control and grapefruit juice group, respectively; P < 0.05). The t(1/2) of (-)-cisapride was significantly increased by grapefruit juice, while this change did not reach significant level for (+)-cisapride. The proportion of pharmacokinetic changes brought about by grapefruit juice was similar for both enantiomers, suggesting non-stereoselective interaction. We found no significant difference in mean QTc intervals between the water and grapefruit juice treated groups. CONCLUSIONS: The pharmacokinetics of cisapride is stereoselective. Grapefruit juice elevates plasma concentrations of both (-)- and (+)-cisapride, probably through inhibition of CYP3A in the intestine. At present, there are no data on whether the enantiomers exhibit stereoselective pharmacodynamic actions. If they do, determination of plasma concentrations of the individual enantiomers as opposed to those of racemic cisapride may better predict the degree of drug interaction, cardiac safety and prokinetic efficacy of cisapride.