苦参碱及氧化苦参碱的药代动力学与药效动力学

以QTc延长率为效应指标,用药代动力学-药效动力学结合模型对苦参碱、氧化苦参碱iv后在免体内的处置和效应动力学作定量分析,两药的血浓时程均符合二房室模型,两药的效应与效应室浓度之间的关系均符合S形E_max模型。两药彼此的药动学和药效学性质均有明显差异,但它们各自的劳动学和药效学性质在所用剂量范围内均为非剂量依赖性。     

TOXIC AND CARCINOGENIC EFFECTS OF PARENTERAL AND PERCUTANEOUS ATP AND ITS IRON COMPLEX

ABSTRACT

The long term effects of percutaneous, subcutaneous and intraperitoneal administration of sodium–ATP (NaATP) and ferric iron–ATP (FeATP) were studied on an animal model. Both compounds induce a generalized lymphoadenitis which in the case of FeATP led to lymphomas. The analytical study of the involved target tissues showed intracellular composition changes that result from the impairment of the cell membrane permeability. The morbidity and mortality rate were higher with FeATP which seems to be the result of two different, in intensity and duration, interactions with the cell plasma membrane. The influence of the changes in cellular calcium homeostasis, and its relationship with carcinogenesis and immuno response are discussed.     

HPLC和~1HNMR分析确定cis－A－和cis－B－羟甲芬太尼的组成和构型

羟甲芬太尼（１）是一个强效的镇痛剂和高亲和、高选择性的阿片μ受体激动剂。通过ＨＰＬＣ和１ＨＮＭＲ分析，ｃｉｓ－Ａ－ｌ被确定为由等量的ｃｉｓ－（＋）－（３Ｒ，４Ｓ，２＇Ｓ）－ｌ和：ｃｉｓ－（—）－（３Ｓ，４Ｒ，２＇Ｒ）－１组成的外消旋体，ｃｉｓ－Ｂ－ｌ被确定为由等量的ｃｉｓ－（—）－（３Ｒ，４Ｓ，２＇Ｒ）－１和ｃｉｓ－（＋）－（３Ｓ，４Ｒ，２＇Ｓ）－１组成的外消旋体。     

冰毒吸食者焦虑抑郁情绪和自我概念的测评及相关分析

目的:了解冰毒吸食者焦虑抑郁情绪和自我概念状况,探讨二者之间的关系,为临床心理干预提供依据。方法:采用抑郁自评量表(SDS),焦虑自评量表(SAS)和田纳西自我概念量表(TSCS)对36例强制戒毒的冰毒吸食者(研究组)和36例健康人群(对照组)进行调查,将结果进行统计学处理分析。结果:(1)研究组SDS,SAS评分明显高于对照组,差别具有统计学意义(P<0.01);(2)TSCS评分比较,研究组除自我批评因子分高于对照组外,其余各因子分均低于对照组,差异具有统计学意义(P<0.01);(3)TSCS与SAS和SDS之间具有高度相关性(r=0.411-0.462,P<0.01)。结论:冰毒吸食者焦虑抑郁情绪明显,表现为消极的自我概念;焦虑抑郁情绪影响自我概念。临床治疗中应关注戒毒者负性情绪和自我概念,采取有效措施帮助他们消除负性情绪,树立积极的自我概念,促进心理康复。     

顶头孢霉229与12的分生孢子及原生质体的形成和再生

头孢菌素产生菌顶头孢霉菌株229的沉没培养或斜面培养都可形成分生孢子,并可用普通滤纸将它们与菌丝及节孢子分开,但是它们成活率极低.这种成活的分生孢子的数量与培养基成分有关.菌丝培养基成分对制备顶头孢霉原生质体有显著影响.用一种MM培养基培养的菌丝,不经巯基化合物预处理,酶解(1%纤维素酶)3小时后,可得到大量原生质体.原生质体的再生频率为1.8～4.6%.与分生孢子形成的菌落相比,原生质体再生菌落的产抗生素能力显示出较大的变异性.本文还讨论了山梨醇与Nikkomycin对菌丝生长形态及原生质体形成的影响.     

LIVER ALCOHOL AND ALDEHYDE DEHYDROGENASE: INHIBITION AND POTENTIATION BY HISTAMINE AGONISTS AND ANTAGONISTS

1. The in vitro effects of histamine, some other Hi- and H₂-receptor agonists and some antagonists were studied on the specific activities and kinetics of rat liver alcohol dehydrogenase (ADH), and cytoplasmic and mitochondrial liver aldehyde dehydrogenase (ALDH). 2. Histamine (H₁- and H₂-agonist) non-competitively inhibited ADH and ALDH, 2-(2-aminoethyl) pyridine (Hi-receptor agonist) non-competitively inhibited ADH. There were no changes of cytoplasmic and mitochondrial liver ALDH activities in the presence of 2-(2-aminoethyl) pyridine. 3. Betazole (H₂-receptor agonist) produced a competitive inhibition of mitochondrial ALDH but not of ADH or cytoplasmic ALDH. 4. Diphenhydramine (H₁-receptor antagonist) non-competitively inhibited ADH at a lower concentration. It stimulated mitochondrial ALDH activity without changes in cytoplasmic ALDH from control values. 5. Burimamide (H₂-receptor antagonist) produced a biphasic and dose-dependent stimulation and non-competitive inhibition of ADH and it non-competitively inhibited ALDH in both cytoplasmic and mitochondrial fractions. Metiamide (H₂-receptor antagonist) non-competitively inhibited all ADH and ALDH of both liver fraction studied. 6. It is concluded that liver ADH and ALDH activity can be altered by compounds which affect both Hi- and H₂-histamine receptors and that these compounds may cause an in vivo potentiation and/or reduction of the toxic effect of ethanol.     

TOXICOKINETICS AND EFFECTS OF FIBROUS AND NONFIBROUS PARTICLES

Chronic inhalation of fibrous and nonfibrous particles by rats at high concentrations results in lung tumor formation if the particles are poorly soluble in the lung. Even rather benign nonfibrous particles such as TiO 2 produce this result. One significant change during a chronic inhalation exposure of poorly soluble particles of low cytotoxicity (PSP) is an impairment of normal clearance mechanisms in the alveolar region of the lung in rats, resulting in a continued buildup to high lung burdens accompanied by chronic alveolar inflammation, fibrosis, and mutational events. Since these are obviously high-dose effects, questions about their extrapolation to humans exposed to much lower concentrations have been raised. Results of key studies reported for chronic inhalation of PSP in rats indicate that mechanisms of PSP-induced lung tumors at high doses do not operate at low dose levels. Furthermore, the existence of two thresholds can be postulated: One is a dosimetric threshold for the endpoint alveolar macrophage-mediated clearance, which is related to lung particle overload. The other is a mechanistic threshold for the endpoint mutation, which is determined by the level of antioxidant defenses to counter-balance reactive oxidant species released by activated inflammatory cells. A no-observed-adverse-effect level (NOAEL) could therefore be based on avoiding alteration of the toxicokinetic of the particles such that the lung burdens stay below the dosimetric threshold. The suggestion that PSP-associated organic compounds (e.g., diesel particulate matter) contribute to the lung tumor responses in rats observed in chronic inhalation studies is not supported by experimental data from in vivo studies. It can be concluded that high-dose rat lung tumors due to PSP should not be used for low-dose extrapolations, and no significant contribution to human lung cancer risk can be predicted from levels of PSP below lung overload. With respect to the pulmonary toxicokinetics of inhaled fibrous particles, the biopersistence of long fibers (>20 µm) which cannot be phagocytized by alveolar macrophages is a key parameter related to long-term carcinogenic effects. Long fibers with a very low biopersistence should not be considered as carcinogenic. Since the clearance kinetics of fibers can generally be described by a biphasic or multiphasic pattern - fast initial and slow final phase - it is essential that the slow phase of the retention kinetics of fibers longer than 20 µm is considered in a biopersistence assay. Based on the results of such assay, fibers can be classified into one of two categories: a biopersistent fiber that cannot be dissolved in the lung within an acceptable time period; or a biosoluble fiber when even long nonphagocytizable fibers will be disappearing rapidly from the lung. However, in addition to biopersistence, it should be mandatory to evaluate fiber toxicity in an appropriate assay relative to a fiber whose long-term effects are well known. Moreover, for organic fibers it is likely that different rules may have to be established for characterization of their toxic and carcinogenic potential.     

珍珠母贝中糖胺聚糖的提取分离纯化

目的:对马氏珍珠母贝中提取、分离得到的糖胺聚糖(glycosam inog lycans,GAG)进行化学组分研究。方法:样品经还原、水解和乙酰化,采用气相色谱-质谱法定性测定。结果:测定出马氏珍珠母贝中经提取、分离得到的GAG中的3种主要成分,其骨架结构分别与(硫酸乙酰)肝素、(硫酸)软骨素和透明质酸相符。结论:马氏珍珠母贝中提取分离的糖胺聚糖中含有肝素、软骨素和透明质酸。     

SODIUM AND NORADRENALINE IN CEREBROSPINAL FLUID AND BLOOD IN SALT-SENSITIVE AND NON-SALT-SENSITIVE ESSENTIAL HYPERTENSION

1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16-18 g/day) and after 7 days of a low salt intake (1-3 g/day). 2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 +/- 0.4 mmol/L vs 145.3 +/- 0.5 mmol/L; P less than 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period. 3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt-sensitive (n = 8) and the non-salt-sensitive (n = 7) subjects, but the changes in plasma NA and PRA were smaller in the salt-sensitive subjects. 4. These results indicate that the sympathetic nervous system is less suppressed in salt-sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.     

PLASMA AND PITUITARY PROLACTIN AND BLOOD PRESSURE IN BROMOCRIPTINE-TREATED SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.     

刺激剂类药物及代谢物的分离鉴定

报道了41种刺激剂的气相色谱和质谱数据以及人尿中原药和它们的游离型和结合型代谢物的分离和鉴定方法。用分辨率高的毛细管气相色谱分离,以灵敏度高专属性好的氮磷检测器检测志愿者24 h尿样中游离型母体药及代谢物。选择部分时间收集尿样进行直接气质联用分析以及采用三氟醋酰化、三甲基硅烷化和两者并用的衍生化方法鉴定母体药及游离型代谢物。尿样酸水解后,再进行以上选择性衍生化,可测定它们的结合型代谢物。     

E-REGULATION AND INTERNET PHARMACIES: ISSUES AND DILEMMAS

ABSTRACT

As online healthcare delivery gains momentum in the new millennium, it is going to pose greater challenges for the regulators internationally so that the consumer's best interest is maintained. It will become increasingly important to identify and inform consumers regarding reputable websites that can address some health-related issues for the consumer. This paper discusses some of the evolving issues and dilemmas facing private sector companies, Internet advertisers, and government regulatory agency's role in promoting public health and safety. Some of the challenges involved in cultivating the benefits of electronic commerce, while at the same time preventing abuse, fraud, and deceptive and dangerous online practices, are also explored.

The paper outlines some of the early efforts of regulatory bodies, particularly the Food and Drug Administration (FDA), to keep abreast of rapidly changing developments and complex issues involved in the growth of “internet pharmacies.” In part, this paper offers a snapshot of the unruly, chaotic birth and nascent development of both an industry and a technology that threaten to outrun the ability of the law and public agencies to monitor and regulate. Some of the issues related to online healthcare delivery are also discussed.     

取代腺嘌呤和腺苷的合成及生物活性

为了探索芳杂环甲基取代腺嘌呤和腺苷的有效合成方法,本文以腺嘌呤和腺苷为原料设计并合成了7个9-取代腺嘌呤(1～7)、6个N⁶,9-双取代腺嘌呤(12～17),3个N⁶-取代腺嘌呤(23～25)、5个N⁶-取代腺苷(18～22),同时合成了3个3-取代腺嘌呤(9～11),共24个化合物,其中23个为未知化合物。对合成的所有腺苷衍生物和部分腺嘌呤衍生物进行了腺苷受体活性筛选。化合物18在大鼠输精管模型上对腺苷受体的激动活性是腺苷的33倍。     

INTERACTIONS BETWEEN METHAQUALONE AND ETHANOL IN RATS AND MICE DURING ACUTE AND CHRONIC STATES

1. The effects of acute and chronic treatment of methaqualone on ethanol preference, the rate of disappearance of ethanol and on toxicity were studied in mice and rats. 2. Acute treatment with methaqualone showed a dose-dependent suppression in the voluntary intake of ethanol in C57B1/6J mice and rats. No significant change in ethanol intake was observed during chronic methaqualone treatment and withdrawal. 3. Methaqualone pretreatment significantly (P < 0.005) delayed the disappearance of ethanol in the blood and brain over a period of 50 to 200 min after a loading dose of 2.0 g/kg, i.p., of ethanol. 4. Methaqualone pretreatment at doses of 140 and 200 mg/kg significantly increased ethanol toxicity by 11% and 28%, respectively. Co-administration of ethanol using 6.0, 7.0 and 8.0 g/kg also reduced the LD₅₀ of methaqualone by 19%, 24% and 40%, respectively. 5. Chronic administration with ethanol decreased the toxicity due to methaqualone. Potentiation of ethanol toxicity by methaqualone may be of clinical importance in view of the narrow range of safety margin of ethanol.     

氨苄青霉素,羧苄青霉素中寡聚物的分离分析

在葡聚糖凝胶ＳｅｐｈａｄｅｘＧ－１０（４０～１２０μｍ）凝胶色谱系统中，用１ｍｏｌ／Ｌ的硫酸胺溶液（ｐＨ７．２）作流动相，实现了对氨苄青霉素、羧苄青霉素高聚物、寡聚物和药物本身的分离，利用ＦＡＢ－ＭＳ、ＨＰＬＣ等分析手段证明，氨苄青霉素、羧苄青霉素中的寡聚物主要为混合二聚体：在氨苄青霉素中主要含开环和闭环二种不同结构的聚合物，在羧苄青霉素中为其Ｄ型和Ｌ型旋光异构体形成的同聚和异聚聚合物。     

黄花夹竹桃次甙甲和次甙乙的强心作用与毒性

本实验用在体猫和豚鼠的衰竭心脏、离体豚鼠心脏和左心房条观察了次甙甲和次甙乙的强心作用与毒性,并与已知强心甙哇巴因和毒毛旋花子甙K进行比较。结果表明,次甙甲和次甙乙都可使猫和豚鼠的衰心泵血功能部分或完全恢复,给药后LV-dp/dt max,LVSP和BP升高,LVEDP和CVP下降,其作用性质与哇巴因和毒毛旋花子甙K相似,安全范围以次甙甲较大,等毒性剂量的次甙甲和次甙乙对离体豚鼠心脏的强心作用均比哇巴因强,给药后2—3分钟差异显著,但三者对离体豚鼠左心房条的正性肌力作用则相似。     

苯丙胺类兴奋剂在德国和欧洲的应用和治疗

背景和目的:概述苯丙胺类兴奋剂(ATS)如苯丙胺、甲基苯丙胺、摇头丸等在欧洲和德国的流行、消费模式和防治措施。在德国使用的非法物质中,大麻至今仍然是消费最广泛的非法药物。值得一提的数据是持续使用12月可卡因的为0.6%,苯丙胺为0.4%,摇头丸和迷幻蘑菇均为0.4%。海洛因、LSD、快克和可卡因的消费仍然限于在特定和更小范围的人群。2007年欧洲校园成瘾药物和其他药物调查项目的结果(the European School Survey Project on Addiction and other Drugs,ESPAD)显示,28%被调查的学生曾经尝试过某种非法药物(大麻、苯丙胺类、摇头丸、LSD、可卡因、快克或海洛因)(Krausetal.2008)。非法药物终生消费率(除了大麻)自2003年以来仍然几乎没有变化(10.0%vs.10.2%).在非法药物中(不包括大麻),苯丙胺类(6%)是最常被尝试的药物(一生中至少一次)。但是,与其它物质比较,苯丙胺类在德国的流行仍然不是非常广泛。闲暇和夜生活等中的药物滥用的预防措施仍然很缺乏。在一些城市(大多数是大城市),青少年中心,药物咨询机构或当地政府的团体项目已经制定了预防措施。他们通过网站或者传单宣传娱乐场所物质滥用的危害。在节日、聚会、夜总会或迪斯科舞厅的这些行动旨在提供药物滥用预防的信息。苯丙胺、甲基苯丙胺和摇头丸是欧洲最常用的非法药物。可卡因使用者的绝对数量可能更高,但就地理分布而言在许多国家一些合成药物仍然是继大麻后最常用的非法物质。而且,在一些国家苯丙胺的使用仍旧是药物滥用问题的重要部分,在治疗需求中占相当大的比例。最近的人群调查提示,欧洲各国家苯丙胺终生使用率(成年人,15-64a)在0到11.7%之间变化。平均3.5%的欧洲成年人报告曾经使用过至少一次苯丙胺。去年药物使用大大降低,欧洲人加权平均数为0.5%。据估计大约1千2百万欧洲人尝试过苯丙胺,大约2百万人在过去的一年使用过药物。要求对苯丙胺类为主的药物使用进行治疗的报道在大多数欧洲国家相对较少,主要在瑞典(34%),芬兰(23%),拉脱维亚(16%)和葡萄牙(11%)占相当大的比例。另四个国家(比利时,丹麦,德国,荷兰)的比例在6%和10%之间,其他国家的比例小于3%。在娱乐场所的药物滥用可提供一个研究使用苯丙胺类和摇头丸等行为的窗口。在这些场所药物滥用的估计数据特别高,多数药物使用发生在周末和假日。安全俱乐部指南旨在减少药物相关问题的发生机会,包括免费提供冷水、快速急救和宣传预防措施。国家专家提供了在夜总会这些措施的实施情况。总的说来,欧洲夜生活场所仅采用有限的预防和减少健康风险和药物使用的简单措施。宣传预防工作在19个国家中的少数夜总会开展。苯丙胺类的使用者通常在门诊药物服务机构获得治疗。在苯丙胺使用历史较为严重的国家中这样的门诊药物服务专门治疗这种类型的药物问题。大多数问题苯丙胺使用者可以在精神诊所或医院接受住院治疗。本文将介绍预防和治疗的方案。