清肝袋泡剂治疗高催乳素血症临床与实验研究

目的：进一步观察清肝袋泡剂对高催乳素血症（ＨＰＲＬ）患者的临床疗效,探讨其作用机制。方法：随机将患者分为治疗组１２０例（清肝袋泡剂）,对照组４０例（溴隐亭）。观察血中催乳素（ＰＲＬ）和相关激素水平及症状变化情况,进行疗效对比。同时通过动物实验对内分泌水平及卵巢、子宫、乳腺的组织形态变化进行同步观察。结果：清肝袋泡剂可显著降低患者血清ＰＲＬ水平,对相关激素有良性调节作用,临床疗效良好,与对照组比较无显著性差异（Ｐ＞０．０５）;动物实验证明能促进卵泡发育,使子宫内膜出现各动情周期的变化,抑制乳腺腺体增生。结论：清肝袋泡剂可有效治疗ＨＰＲＬ。     

Analysis of Drug/Plasma Protein Interactions by Means of Asymmetrical Flow Field-Flow Fractionation

Purpose. The applicability of Asymmetrical Flow Field-Flow Fractionation (Asymmetrical Flow FFF) as an alternative tool to examine the distribution of a lipophilic drug (N-Benzoyl-staurosporine) within human plasma protein fractions was investigated with respect to high separation speed and loss of material on surfaces due to adsorption. Methods. Field-Flow Fractionation is defined as a group of pseudo-chromatographic separation methods, where compounds are separated under the influence of an externally applied force based on differences in their physicochemical properties. This method was used to separate human plasma in its protein fractions. The drug distribution in the fractions was investigated by monitoring the fractionated eluate for drug content by fluorescence spectroscopy. Results. Human plasma was separated into human serum albumin (HSA), high density lipoprotein (HDL), ₂-macroglobulin and low density lipoprotein (LDL) fractions in less than ten minutes. Calibration of the system and identification of the individual fractions was performed using commercially available protein reference standards. The influence of membrane type and carrier solution composition on the absolute recovery of N-Benzoyl-staurosporine and fluorescein-isothio-cyanate-albumin (FITC-albumin) was found to be quite significant. Both factors were optimized during the course of the investigations. N-Benzoyl-staurosporine was found to be enriched in the fraction containing HSA. Conclusions. If experimental conditions are thoroughly selected and controlled to suppress drug and plasma protein adsorption at the separation membrane, Asymmetrical Flow FFF shows high recoveries and fast separation of human plasma proteins, and can be a reliable tool to characterize drug / plasma protein interactions. For analytical purposes it has the potential to rival established technologies like ultracentrifugation in terms of ease-of-use, precision, and separation time.     

二硫化碳作业女工早期胚胎损伤的剂量反应关系

目的 探讨女工二硫化碳（ＣＳ２）接触水平与胚胎早期发育障碍之间的剂量－反应关系。方法 前瞻观察生育女工妊娠所需的月 经周期数;收集每个月经周期胚胎植入期尿样,检测绒毛膜促性腺激素含量;监测女工作业地点ＣＳ２浓度。结果 ２５７名接触组经临床确诊妊娠的女工,各月经周期妊娠机率低于３６６名对照组女工,时间妊娠率随女工ＣＳ２接触水平（ＣＳ２接触浓度以ＣＳ２接触工龄）升高而降低：妊娠率＝０．７０３３－０．０     

Erbium filtration: a cost-effective, dose-reducing filter which maintains abdominal image quality

The current study investigated the effect of erbium filtration on an anteroposterior abdominal image. The radiation dose reductions achieveable and the costeffectiveness of this filter were also evaluated. An assessment of the radiation dose delivered employing either the standard total filtration (3 mm Al equivalent) or 0.1 mm of erbium filtration added to the standard filtration was undertaken on 21 patients. Image quality was assessed using the Commission of European Communities (CEC) criteria. Significant reductions of 64.6 % in entrance surface (p = 0.0001) and 23.4 % in effective dose (p = 0.0099) were recorded with erbium filtration. Image quality was maintained and the cost per manSievert saved was ￡ 128. More widespread use of this dose reducing filter is advocated. Received: 7 August 1998; Revised: 19 February 1999; Accepted: 19 April 1999     

骨转移癌不同分割放射治疗比较

目的比较不同分割放射治疗骨转移癌患者的时间效应,评价不同分割放疗的止病疗效。材料与方法对1992年5月～1997年5月我院收治的123例骨转移癌患者分别给予常规分割组、超分割组及大剂量低分割组不同的放射治疗,观察各组姑息止痛的放疗有效率．结果放疗1周时,止痛有效率为5．41％、10．3％及65．2％;放疗结束时为70．3％、77．3％与77．3％;放疗结束后3个月为65．0％、67．6％及74．2％．经统计学分析发现放疗1周时大剂量低分割组止痛有效率与其它组比较有明显差异。结论大剂量低分割放疗止痛率高,疗效出现早,而放疗结束时及结束后3月3组止病率无差异。故在骨转移癌的放疗中可考虑采用先大剂量低分割放疗后继常规或超分割的放疗方式。     

槲皮素对培养人视网膜色素上皮细胞增生及DNA合成的影响

目的研究槲皮素(quercetin, QUE)对培养人视网膜色素上皮(retinal pigment epithelium, RPE)细胞增生和DNA合成以及对表皮生长因子(epidermal growth factor, EGF)促RPE细胞增生和DNA合成作用的影响。方法用细胞计数和3H-胸腺嘧啶核苷(3H-thymidine, 3H-TdR)掺入方法,观察不同浓度(200、100、50、1μmol/L)的QUE和最大浓度的QUE(200μmol/L)在不同作用时间（24-168小时）,分别单独或与EGF共同作用时,对RPE细胞增生及DNA合成的影响,排除着色的死细胞,用活细胞计数法判断药物的细胞毒性作用。结果QUE 200μmol/L具有最强的抑制效应,48小时时抑制效应已明显出现,96小时时抑制达到高峰。与QUE单独作用相比,QUE对EGF的促RPE细胞增生效应能产生更强的抑制。QUE无细胞毒性作用,各实验组细胞活力均在85.00%以上。结论QUE以剂量依赖和时间依赖的方式抑制RPE细胞的增生,尤其是由EGF刺激的增生,并且对培养的RPE细胞无细胞毒作用。(中华眼底病杂志,1999,15:27-29)     

Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers

Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence. Received: 9 February 1998/Final version: 8 May 1998     

Flexure dose: the low-dose limit of effective fractionation

Total radiation dose often can be increased without subsequent increases in the severity of tissue injury by using reduced doses per fraction. The flexure dose, df, is defined as the largest fractional dose for which further fractionation produces no significant change in the total dose required to reach a specified effect level. Thus, df is clinically relevant in that it represents the limit of effective dose fractionation. For those tissues in which injury reflects depletion of a critical proportion of target cells, the flexure dose is a measure of the extent of the initial, nearly linear portion of the dose-survival curve. More generally, the flexure dose is a measure of the extent of the initial, nearly linear portion of a dose-response curve in organized tissue, whatever its relationship to clonogenic target cells might be. Several quantitative expressions for df are derived. The characteristic common to these is that each defines the flexure dose as a multiple of the ratio alpha/beta of the parameters of the linear-quadratic model of cell survival or dose response, where the multiple is a measure of experimental or statistical resolution. These multiples tend to fall within a limited range, thereby defining the "region of flexure" via the inequality 0.05 (alpha/beta) less than or equal to df less than or equal to 0.15 (alpha/beta). Estimates of the region of flexure are presented for a variety of normal and neoplastic tissues.     

Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: time course of appearance of recently synthesized proteins in synaptic junctions.

Previous studies have led to the hypothesis that some protein constituents of postsynaptic membrane specializations are locally synthesized near postsynaptic sites. The present study focuses on one prediction of this hypothesis, specifically, that if some proteins of the postsynaptic membrane specialization are locally synthesized, then the delay between synthesis and assembly into synaptic junctional membrane could be short. We evaluate the time course of appearance of recently synthesized protein in synaptic junctions by pulse-labeling hippocampal slices maintained in vitro with radiolabeled protein precursors, and then isolating subcellular fractions enriched in synaptic plasma membranes (SPM) and synaptic junctional complexes (SJC). We report that there is no evidence of a delay in the appearance of recently synthesized proteins in SPM and SJC fractions. Labeled proteins could be detected as early as 15 min after the initiation of the pulse-labeling period, and the extent of labeling increased monotonically thereafter. The labeling could not be accounted for by contamination of synaptic membrane fractions with other membranes, because the relative specific activity of the SPM and SJC fractions was the same or higher than that of the less pure fractions from which these synaptic fractions were derived. One-dimensional PAGE-fluorography was used to provide an initial characterization of which proteins were labeled in SJC fractions. We found that the most prominent labeled bands were at apparent molecular weights of approximately 43-44, 55-56, and 60 kd, with more lightly labeled bands at about 38 and 116 kd. In some preparations, there was a labeled doublet at about 36-38 kd. There were also other lightly labeled bands at other molecular weights. These bands were much less heavily labeled than the bands at 43-44, 55-56, and 60 kd, however. There was little labeling in the molecular weight range of the "major psd protein" (the alpha subunit of CAM-kinase), although there was diffuse labeling throughout the 45-52 kd region. These results are consistent with the hypothesis that some of the protein constituents of the postsynaptic junctional complex are synthesized by polyribosomes which are selectively localized beneath synaptic junctions.