Tissue distribution of 14C-diazepam and its metabolites in rats

We have kinetically investigated the tissue distribution of 14C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of 14C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence.     

Nicotine binding to brain tissue from drug-naive and nicotine-treated rats

Two nicotine binding sites with dissociation constants for nicotine of approximately 3 nM and 12 μM respectively have been found in homogenates of rat hippocampus, hypothalamus, parietal cortex and mesencephalon, the greatest density of high affinity binding sites being in parietal cortex (30.0 ± 3.0 fmol (mg protein)^?1), the lowest in hypothalamus (16.1 ± 1.0 fmol (mg protein)^?1). The density of the low affinity sites (approx. 20 pmol (mg protein)^?1) did not show any regional variation. Neither site was present in homogenates of medulla oblongata. The accumulation of radioactivity following the subcutaneous administration of [³H]nicotine (0.4 mg kg^?1) was rapid, the highest concentrations being found in the brain regions with the highest density of high affinity binding sites. Medulla oblongata did not accumulate radioactivity above the concentration found in plasma. The chronic administration of nicotine (0.4 mg kg^?1 s.c. daily for 39 days) had no significant effects on [³H]nicotine binding to brain tissue or its accumulation into brain following subcutaneous administration. It is concluded that nicotine readily passes from plasma into brain tissue and is accumulated in the areas containing high affinity binding sites for the compound. It is also concluded that the biochemical and behavioural effects reported previously in response to the chronic daily administration of nicotine do not depend upon changes in its uptake or binding by brain tissue.     

Differential and non-uniform tissue and brain distribution of two distinct 14C-hexachlorobiphenyls in weanling rats.

Excretion and tissue retention of a coplanar and a non-coplanar hexachlorobiphenyl (HxCB) were determined 48 h after a single intraperitoneal (ip) dose of 8 mg/kg radiolabeled [14C]-HxCBs to weanling male and female Long-Evans rats. The objective was to understand the involvement of initial target organs of chlorobiphenyl (CB) accumulation following acute exposure in immature animals. During the short interval, both HxCBs remained sequestered predominantly in mesenteric fat (compared to subcutaneous fat) and less than 1% of the doses were excreted. Excretion was 4- to 8-fold lower than adult rats. Coplanar CB 169 (3,3',4,4',5,5'-HxCB) did not accumulate appreciably in the brain, but was retained at 3-fold higher levels in the liver than was non-coplanar CB 153 (2,2',4,4',5,5'-HxCB). Accumulation of 14C-CB 153 in brains was 4- to 9-fold higher than that of 14C-CB 169 and was adequate to detect non-uniform distribution in serial cryostat sections by phosphor imaging autoradiography. The autoradiographs showed a higher CB 153-derived radioactivity associated with fiber tracts throughout the brain. Specifically, the corpus callosum, internal and external capsules, medial lemniscus, tegmentum of the mesencephalon and metencephalon, and cerebellar peduncles showed significantly higher 14C-CB 153 than the other structures. The 14C-CB 153 was not found in the ventricular system and vascular spaces. These results suggest for the first time that an ortho-substituted PCB congener accumulated preferentially in brain in a structure-specific manner when compared to a non-ortho-substituted PCB congener.     

太平洋牡蛎多糖的提取、分离和结构分析

目的　从太平洋牡蛎(Crassostrea gigas)肉中提取和分离纯化多糖,并对其基本理化性质和结构组成进行分析。方法　将牡蛎鲜肉制成丙酮粉,依次采用室温水,60 ℃热水和稀碱提取牡蛎粗多糖,对其总糖含量、蛋白含量和单糖组成进行分析。采用DEAE Sepharose FF阴离子交换和Sephacryl S-400凝胶柱层析对粗多糖进行分离纯化,并对获得的纯化组分采用红外光谱 (IR)、甲基化、气质联用 (GC-MS)、电喷雾质谱 (ESI-MS) 和核磁共振波谱 (NMR) 等方法进行化学结构分析。结果　从牡蛎肉中提取得到了3种牡蛎粗多糖,单糖组成都只含有葡萄糖 (Glc)。对粗多糖进一步分离,得到了5种多糖纯化组分。对水溶性多糖纯化组分 MC-11 的结构进行了分析,表明其是以 →4)-α-D-Glc-(1→ 为主链,含有 →3,4)- β-D-Glc-(1→和 →2,4)- β-D-Glc-(1→ 分支的 D-吡喃型葡聚糖,相对分子质量为1299 kDa。结论　从太平洋牡蛎肉中分离纯化得到了5种多糖组分,并采用多种方法确定了1种纯化组分 MC-11 的结构,为牡蛎多糖结构与活性关系的深入研究提供了基础。     

石花多糖抗辐射有效部位的提取分离及检测

目的:对具有抗辐射作用的石花多糖粗品进行提取、分离和纯度检测.方法:将梅花衣科植物石花(Parmelia tinctorum Despr)水提、醇沉后,经AB-8树脂脱色和三氯乙酸除蛋白,再用DE22纤维素柱分离,冷冻干燥后得浅灰色粉末多糖;对石花多糖有效组分进行纸层析分析和玻璃纤维纸电泳纯度检查.结果:纯度检查不多于3个斑点.结论:石花多糖有效部位为相对单一组分.     

缢蛏多糖的提取、分离和结构分析

目的从缢蛏中提取和分离纯化多糖,对其基本理化性质和结构组成进行分析。方法依次采用100℃热水提和碱提方法从缢蛏中提取粗多糖,采用Q Sepharose Fast Flow强阴离子交换柱层析和Sephacryl S-300凝胶柱层析对粗多糖进行分离纯化,并对其总糖、蛋白含量,相对分子质量和单糖组成进行分析。对多糖纯化组分采用甲基化、气质联用(GC-MS)、红外光谱(IR)和核磁共振波谱(NMR)进行化学结构解析。结果从缢蛏中经热水提粗多糖(YC-S)和碱提粗多糖(YC-J)均为葡聚糖,进一步分离纯化得到了4种水溶性多糖组分。对其中1种热水提多糖纯化组分YC-S2采用高效液相凝胶色谱法测得其相对分子质量为482kD,且色谱峰单一对称,表明其具有较高的纯度。结构分析表明,YC-S2是1种以α-(1→4)Glc为主链,含有少量的β-(1→3,4)和β-(1→4)分支的D-吡喃型葡聚糖。结论从缢蛏中提取分离得到了4种多糖组分,并初步确定了1种水溶性葡聚糖的结构,为缢蛏多糖结构和活性的深入研究提供了基础。     

一种多棘海盘车内脏多糖的提取分离和结构表征

目的　从多棘海盘车(Asterias amurensis)内脏中提取、分离纯化多糖,并对其基本理化性质和结构进行表征。方法　采用沸水提取与酶解联用的方法从多棘海盘车内脏脱脂粉中提取粗多糖;采用Q Sepharose FF强阴离子交换和Sephacryl S-100凝胶渗透色谱对粗多糖进行分离纯化;采用硫酸-苯酚法、Folin-酚法、高效凝胶渗透色谱-十八角激光散射仪(HPGPC-MALLS)和高效液相色谱(HPLC)分别进行总糖含量,蛋白含量,分子量和单糖组成进行分析;采用甲基化、红外光谱(IR)、气质联用(GC/MS)和一维、二维核磁共振波谱(NMR)法对纯化多糖结构进行表征。结果　从多棘海盘车内脏中提取粗多糖的收率为3.3%。经过离子交换和分子排阻色谱分离纯化,得到一种分子量均一的多糖组分 F2-A,该多糖主要由葡萄糖(Glc)组成,其糖含量为97.6%,分子量为2708 kDa,是一种以α-(1-4)-Glc为主链并含有少量β-(1-3,4)分支的海星内脏来源葡聚糖。结论 从多棘海盘车内脏中纯化得到一种高分子量、结构独特的葡聚糖,为将来从事其结构和生物活性关系的研究提供了有用信息。     

Lead, zinc, and copper levels in intraocular brain tissue grafts, brain, and blood of lead-exposed rats

Adult female Sprague-Dawley rats were exposed to various concentrations of lead acetate for different lengths of time. Six weeks exposure to lead acetate at concentrations of 0, 0.125, 0.25, 0.5, 1, and 2% in the drinking water, gave rise to brain and blood lead levels that were highly correlated with the lead concentration in the drinking water. When animals were exposed to 1% lead acetate for different lengths of time, an apparent delay in the rate of lead transport into the brain was seen during the first day. However, if animals were exposed for longer time periods, brain lead levels increased faster than did the blood levels. Pieces of fetal cortex cerebri were grafted to the anterior eye chamber of host animals exposed to either 1% lead acetate or to sodium acetate. Six weeks after grafting, the lead concentration in the lead-exposed grafts were 31.6 mg/kg dry wt, as compared to 6.4 mg/kg dry wt in sodium acetate control grafts. However, grafts from both groups had lead levels that were approximately five times higher than in cerebral cortex “punches” from corresponding areas of the host brains. Furthermore, zinc and copper levels were also higher in the grafts as compared to punches of in situ cortex. Taken together with previous reports on animal and human lead exposure, these data indicate that oral lead intake in adult rats bearing intraocular brain grafts yields blood and brain levels which are physiologically relevant to problems of clinical lead toxicity.     

不同来源麒麟菜多糖的提取分离和结构比较△

目的 从不同来源麒麟菜中提取分离多糖,分析其理化性质,比较其结构差异。 方法 将6种麒麟菜依次采用冷水和80℃热水提取,提取液经乙醇沉淀、透析及浓缩冻干后获得麒麟菜多糖;分别采用硫酸-苯酚法、Folin-酚法、离子色谱法 (IC)、高效液相色谱法 (HPLC) 等对其总糖、蛋白质、硫酸根含量、分子质量和单糖组成等理化性质进行分析,并采用傅里叶变换红外光谱(FTIR)和核磁共振碳谱(13C-NMR)对其结构进行比较。 结果 从6种麒麟菜中提取获得12种硫酸多糖,其得率在20%~35%之间,其总糖、蛋白质和硫酸根含量分别在55%~75%,2.4%~8.9%和19.9%~35.1%之间,多糖分子量在238~861kDa之间。单糖组成分析表明,各多糖主要由半乳糖以及少量葡萄糖或者木糖组成。EMP-C,EMI-C,EST-C,ESI-C,EDT-C,EST-H,ESI-H,EDT-H主要为ι -卡拉胶,EMP-H,EMI-H,EGH-H,EGH-C主要为κ-卡拉胶。结论 不同来源麒麟菜多糖的结构不同,为不同结构卡拉胶藻源的选择提供了重要参考。     

茶叶中茶多酚提取分离技术的研究进展

简单介绍了茶叶中茶多酚和咖啡因的药理活性以及茶叶有效成分的组成和几种主要儿茶素类化合物的结构,分析探讨了提取分离废弃茶叶的原因和意义,并综述了近年来国内外有关茶叶中茶多酚提取分离技术的研究进展,包括溶剂提取法、离子沉淀法、超声波提取法、超临界流体萃取法、微波辅助萃取法、柱色谱法、大孔吸附树脂法和高速逆流色谱法,通过不同的实验过程对不同技术手段的应用及特点进行概述,并对这一研究领域的发展前景和发展方向做出展望。     

糖槭叶中皂苷的提取分离条件探讨

目的：研究糖槭叶中皂苷的提取分离条件,为糖槭中皂苷的开发提供科学依据。方法：乙醇浸渍提取法,大孔吸附树脂分离法和薄层色谱法（TLC）。结果：在大孔吸附树脂分离过程中,用10％乙醇作流动相可以分离得到糖、皂苷、香豆素;用30％乙醇作流动相可以分离得到糖、皂苷、香豆素;用50％乙醇作流动相可以分离得到糖、皂苷、香豆素、黄酮苷;用70％乙醇作流动相可以分离得到糖、皂苷;用90％乙醇作流动相可以分离得到皂苷。结论：80％乙醇浸渍法提取,大孔吸附树脂分离皂苷部位方法最佳。     

A pharmacodynamic study of [14C]thiourea toxicity in mature,immature, tolerant,and nontolerant rats

Radioautographic localization of [¹⁴C]thiourea (TU) in rat lung 24 hr post ip administration indicates uniform distribution in alveolar walls. Lung parenchymal tissue may, therefore, be a target area for TU binding and toxicological effects. Immature and tolerant rats bind less radioactivity from [¹⁴C]TU in their lungs than do mature or nontolerant rats. This may partially explain the refractoriness of these animals to the lethal pulmonary edematogenic effect of TU. Differences in binding characteristics or subcellular localization of [¹⁴C]TU were not observed. Immature, mature, tolerant, and nontolerant rats all excrete urinary [¹⁴C]TU in the same amount and at the same rate. If an active intermediate is responsible for the toxicological effect of TU in the lung, then it is probably not formed by liver drug microsomal metabolism since induction of this system with phenobarbital did not alter lung binding. In addition, tolerance to the toxic lung effect of TU does not appear to involve enhanced oxidative inactivation by the liver since pretreatment with TU produced no change in hepatic cytochrome P-450. The possibility remains, however, that formation of a labile metabolite may occur in the lung itself.     

Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP-424391 in rats.

CP-424391, 2-amino-N-[3aR-benzyl-2-methyl-3-oxo-2,3,3a,4,6,7-hexahydro-pyrazolo[4,3-c]pyridin-5-yl)-1R-benzyloxymethyl-2-oxoethyl]-isobutyramide, is an orally active growth hormone secretagogue currently being developed. In this study, we investigated the metabolic fate and disposition of radiolabeled CP-424391 in rats. Following 15 mg/kg single oral administration to Sprague-Dawley rats, 91% of the radiolabeled dose was recovered. Feces was the major route of excretion: 77% of the dose recovered in feces of the female rat and 84% in the male. Excretion in the urine was 15% in the female rat compared with 7% in the male. Both fecal and urinary metabolic profiles were consistent in both genders. The metabolic pathways of CP-424391 were oxidation at the benzyl group of the O-benzylserine moiety, N-demethylation of pyrazolidine, and/or O-debenzylation. In circulation, CP-424391 was absorbed within the first hour to an average apparent C(max) of 1.44 microg/ml. CP-424391 accounts for about 40% of radioactivity area under the plasma concentration-time curve and C(max) in circulation. The plasma terminal elimination half-life of CP-424391 was 2.4 h and for total radioactivity was 2.8 h. The radioactivity was widely distributed in all tissues except for the central nervous system. [(14)C]CP-424391 radioactivity was eliminated from most tissues by 9 h with the exception of liver, skin, and uvea. By 168 h, [(14)C]CP-424391 radioactivity remained localized only in the uvea.     

The metabolism of 14C-DDT, 14C-DDD, 14C-DDE and 14C-DDMU in rats and Japanese quail

Abstract

1. The metabolism and excretion of ¹⁴C-DDT, ¹⁴C-DDD, ¹⁴C-DDE and ¹⁴C-DDMU were compared in male rats and male Japanese quail after i.p. injection.

2. The rate of excretion of radioactivity was greater in the rat than in the quail for all compounds except DDMU. Skin and fat were major sites of residual radioactivity in both species, the compound administered and DDE accounting for most of the radioactivity except in the case of DDMU.

3. The four radiolabelled compounds were all present in significant quantities in excreta of both species in unchanged forms.

4. The metabolic patterns for DDT and DDD were similar in rat and quail, except that the rat formed 2,2-di(4-chlorophenyl)ethanol (DDOH) from DDT while the quail did not.

5. Rat and quail metabolized DDE and DDMU differently. Ring-hydroxylated derivatives of DDE were formed only in the rat and analogous metabolites of DDMU were produced only by quail.

6. Both species produced di(4-chlorophenyl)acetic acid as a metabolite of all four compounds administered, although the formation was generally less and slower in quail than rat.

7. Comparative metabolism of DDMU with the other compounds indicated that this compound is not a metabolic intermediate in the metabolism of DDT in either rat or quail.     

The metabolism of 14C-DDT, 14C-DDD, 14C-DDE and 14C-DDMU in rats and Japanese quail

The metabolism and excretion of 14C-DDT, 14C-DDD, 14C-DDE and 14C-DDMU were compared in male rats and male Japanese quail after i.p. injection. The rate of excretion of radioactivity was greater in the rat than in the quail for all compounds except DDMU. Skin and fat were major sites of residual radioactivity in both species, the compound administered and DDE accounting for most of the radioactivity except in the case of DDMU. The four radiolabelled compounds were all present in significant quantities in excreta of both species in unchanged forms. The metabolic patterns for DDT and DDD were similar in rat and quail, except that the rat formed 2,2-di(4-chlorophenyl)ethanol (DDOH) from DDT while the quail did not. Rat and quail metabolized DDE and DDMU differently. Ring-hydroxylated derivatives of DDE were formed only in the rat and analogous metabolites of DDMU were produced only by quail. Both species produced di(4-chlorophenyl)acetic acid as a metabolite of all four compounds administered, although the formation was generally less and slower in quail than rat. Comparative metabolism of DDMU with the other compounds indicated that this compound is not a metabolic intermediate in the metabolism of DDT in either rat or quail.     

姜黄素的提取、分离与测定

本文探讨了微波辅助提取姜黄素的最佳工艺条件,将其3种成份分离的分离条件及用HPLC法进行其含量的测定.结果 表明其最佳工艺条件为:辐射功率400 w,辐射时间为3 min,溶剂为75%乙醇溶液,剂料比为1:20.利用薄层色谱法筛选的最佳淋洗剂的组成为氯仿-甲醇-冰醋酸(125:5:2).HPLC法测定姜黄素在5～100 mg·L-1的范围内呈线性关系(r=0.99935),样品中姜黄素含量平均为3.2135%,约占总姜黄素的50%.     

Mast cell subtypes from human lung tissue: their identification, separation, and functional characteristics

The contribution of mast cell subtypes and their different mediators to the pathogenesis of chronic obstructive lung diseases (COLD) has not yet been established. In the present study, enzymatic digestion, centrifugal elutriation and Percoll gradient centrifugation were used to obtain two populations of mast cell subtypes from human lung tissue. Mast cell subtypes were challenged with anti-human IgE, propranolol, compound 48/80, or opsonized zymosan. Both subtypes were able to release histamine, but differed in the amount of the amine release. Only the formalin-sensitive and alcian blue-positive type (FS-AB) released histamine on challenge with opsonized zymosan. The same subtype was able to release leukotriene C4 (LTC4) after challenge with anti-human IgE. The other subtype, the formalin-insensitive and alcian blue-positive type (FI-AB), did not respond to opsonized zymosan and did not release LTC4 after challenge with anti-human IgE. Stimulation with propranolol or compound 48/80 did not release histamine from the FS-AB mast cells while the FI-AB mast cells released only about 10% of their histamine content upon challenge with these secretagogues.