Chronic opioid treatment of neuroblastoma X dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K+ currents

Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via G_s regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K⁺ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the G_s/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.     

肿瘤转移相关蛋白在甲状腺乳头状腺癌伴淋巴结转移组织中的原位表达研究

利用免疫组化ＡＢＣ法，研究甲状腺乳头状腺癌，甲状腺腺瘤和正常甲状腺组织中的肿瘤转移相关基因蛋白ＣＤ４４ｖ６，ＥＧＦＲ，转移抑制基因ｎｍ２３－Ｈ１和抑癌基因ｐ５３蛋白的原位表达。结果发现ＣＤ４４ｖ６和ＥＧＦＲ表达上调与肿瘤转移密切相关（Ｐ＜０．０５，Ｐ＜０．０１），而ｎｍ２３－Ｈ１的表达与肿瘤转移抑制密切相关（Ｐ＜０．０１）。这提示肿瘤转移相关基因和转移抑制基因之间的表达失衡是甲状腺乳头状腺癌易发生转移的重要原因。     

米非司酮配伍卡前列甲酯89例与米非司酮配伍米索前列醇110例终止早期妊娠的比较

目的：比较米非司酮配伍卡前列甲酯与米非司酮配伍米索前列醇终止早期妊娠的疗效。方法：妊娠≤４９ｄ孕妇１９９例，年龄２６±５ａ，随机分Ａ组８９例，Ｂ组１１０例。２组均用米非司酮２５ｍｇ，ｂｉｄ，３ｄ，于ｄ４，Ａ组阴道后穹窿置卡前列甲酯栓１ｍｇ。Ｂ组米索前列醇ｐｏ，６００μｇ。结果：Ａ和Ｂ组完全流产率各为８３％和９３．６％，经Ｘ２检验，Ｐ＜０．０５；胎囊排出时间，Ａ组４±５ｈ，Ｂ组３±６ｈ，２组无显著差异。结论：米非司酮配伍米索前列醇的抗早孕效果优于配伍卡前列甲酯。     

Cannabinoid receptor down-regulation without alteration of the inhibitory effect of CP 55,940 on adenylyl cyclase in the cerebellum of CP 55,940-tolerant mice

The objective of this study was to determine whether the development of tolerance to CP 55,940, a potent cannabinoid agonist, was due to changes in the receptor or second messenger system. ICR mice treated with CP 55,940 (2 mg/kg) twice a day for 6 and one-half days developed a high degree of tolerance to the pharmacological effects of CP 55,940. The ability of CP 55,940 to produce motor hypoactivity, hypothermia and immobility was reduced 163-, 97- and 19-fold, respectively. Evaluation of 3H-CP 55,940 binding to rat brain membranes indicated no difference in receptor affinity between the vehicle- and CP 55,940-treated animals. However, these binding studies revealed a 50% decrease in receptor number in the cerebellum of the CP 55,940-tolerant mice. Although cAMP is generally considered to be the second messenger for cannabinoid receptors, little difference was observed in the inhibitory effects of CP 55,940 on adenylyl cyclase activity in cerebellum between vehicle and drug-treated mice. However, there was an increase in receptor mRNA which suggests a compensation for receptor loss. There are several possible explanations for these results. There may be sufficient spare receptors such that CP 55,940-tolerant mice are capable of producing a maximal effect on the second messenger system. On the other hand, one could conclude that cannabinoid receptor down-regulation does not account for the development of tolerance to all of the effects of CP 55,940 in mice.     

氟罗沙星片剂,胶囊剂的人体药物动力学和相对生物利用度研究

9名男性健康自愿受试者采用三交叉单剂口服国产氛罗沙星片剂、胶囊和进口氟罗沙星片剂各400mg的药代动力学参数比较。血、尿药浓度用HPLC检测．结果表明：体内过程符合一室模型，主要药代动力学参数分别为：AUC：82.30±14．30、81．13±8．45与83．92±14.27h·mg／L；Cmax：4．71±0．83、4．67±0．51与4．86±0．89mg／L；Tmax：1．88±0．44、1．90±0．39与1．92±0．23h；T1／2ke：11．02±0．96、10．93±0．68与10．86±0．82h；V／F（c）：79．08±13．31、78.42±8．70与76．39±12．93L；Cl／F：5．00±0．98、4．98±0．52与4．88±0．73L／h。服药48h的尿中原型药排出率分别为给药量的57．4％，55．9％和60．7％。国产氧罗沙星片剂和胶囊口服后药物动力学参数与进口片剂相仿．其相对生物利用及分别为98.07％与96．68％。     

实验国际学校学生膳食及营养状况的调查

本文对南京实验国际学校369名6～11岁学生进行了膳食及营养状况的分析研究。结果表明：该校学生膳食中除视黄醇、钙及锌（9～11岁组）不足外，其余营养素和热能均超过推荐供应量。蛋白质量足质优。脂肪在一天总热能中比例较高．达到30％左右。该校学生营养过剩发生率达18．4％．提示该校食堂要注意学生膳食的合理调配．防止学生摄入过多脂肪和热能；同时建议增加含钙、锌高的食物供给，以补充其不足。     

广东省梅县乡(镇)卫生院卫生人力资源的现状调查分析

乡(镇)卫生院是农村三级医疗预防保健网的中心环节,是我国农村实现“2000年人人享有卫生保健”的关键。本文通过对广东省梅县乡(镇)一级卫生院卫生人力状况的调查分析,结果表明,目前该县乡镇卫生院的机构稳定,卫技人员占编比例合理,年龄较轻,成为今后农村卫生院发展的优势。但存在着卫生技术人员的总体数量不足,素质较差,各类专业技术人员的构成比例失调和层次分布不合理等问题,同时提出了如何加以改善的对策措施。     

双光气对大鼠肺损伤的研究

研究了双光气染毒后不同时间大鼠支气管肺泡灌洗液（ＢＡＬＦ）成分及肺形态学改变。结果表明，双光气染毒后，ＢＡＬＦ成分的变化程度与肺形态改变密切相关ＢＡＬＦ成分分析可作为动物实验中探测双光气所致肺损伤的有力手段。     

Evidence that [3H]-alpha,beta-methylene ATP may label an endothelial-derived cell line 5'-nucleotidase with high affinity.

1. In membranes prepared from a permanent cell line of endothelial origin (WEC cells), [3H]-alpha, beta-methylene ATP ([3H]-alpha, beta-meATP) labelled high (pKd = 9.5; Bmax = 3.75 pmol mg-1 protein) and low (pKd = 7.2; Bmax = 23.3 pmol mg-1 protein) affinity binding sites. The high affinity [3H]-alpha, beta-meATP binding sites in the WEC cell membranes could be selectively labelled with a low concentration of the radioligand (1 nM). In competition studies performed at a radioligand concentration of 1 nM, 88.6% of the sites possessed high affinity (pIC50 = 8.26) for alpha, beta-meATP. 2. The high affinity [3H]-alpha, beta-meATP binding sites appeared heterogeneous since in competition studies a number of nucleotide analogues (alpha, beta-meADP, ATP, ADP, AMP, GTP, GppNHp, GMP) and adenosine identified two populations of the sites labelled by 1 nM [3H]-alpha, beta-meATP. The proportion of sites with high affinity for these compounds was found to vary between 42 and 69%. 3. Approximately 60-69% of the binding sites labelled with 1 nM [3H]-alpha, beta-meATP possessed high affinity for alpha, beta-meADP (pIC50 = 8.87), AMP (pIC50 = 7.12), GMP (pIC50 = 7.34), UTP (pIC50 = 6.12), GTP (pIC50 = 7.59), GppNHp (pIC50 = 7.35) and adenosine (pIC50 = 5.45).(ABSTRACT TRUNCATED AT 250 WORDS)     

胎盘组织液氨基酸的含量测定及层析鉴别

本文采用层析法进行鉴定,用氨基酸分析仪测氨基酸的含量,为胎盘组织液的质量标准提供可靠依据。本法准确率为99%。