光化学作用对肿瘤细胞胞吞大分子的释放

目的观察不同光敏剂在肿瘤细胞内的分布,以及光化学作用对肿瘤细胞胞吞大分子的释放作用.方法使用激光共聚焦显微镜观察ALA、ALA-HE、HMME、TPPSa2在肿瘤细胞SW480、K562的胞内分布,使用FITC-右旋糖酐观察肿瘤细胞对荧光标记大分子的胞吞作用,通过光照激发光敏化细胞,动态观察光化学作用前后胞吞大分子FITC-右旋糖酐的胞内分布变化.结果ALA、ALA-HE、HMME、TPPSa24种光敏剂均表现为胞质分布,核内分布少.ALA、ALA-HE的胞内分布主要表现为胞质内的弥散性荧光.HMME则表现为胞质内颗粒状荧光与弥散荧光同时存在.TPPSa2为典型的胞质内颗粒状荧光分布.光敏剂在SW480、K562两种肿瘤细胞的胞内分布没有明显差异.光照激发不同光敏剂对肿瘤细胞胞吞FITC-左旋糖酐的胞内分布影响不同.由TPPSa2及HMME活化而产生的光化学作用表现出明显的荧光颗粒重分布,ALA、ALA-HE则对胞吞荧光无明显重分布作用.结论不同光敏剂因其不同的理化性质而表现为不同的胞内分布.光化学作用可对肿瘤细胞胞吞大分子产生胞吞释放作用,其作用机制可能与光化学作用对胞吞泡的破坏有关.     

皮下环精索封闭疗法治疗急性附睾-睾丸炎疗效观察

目的评价急性附睾-睾丸炎皮下环精索封闭疗法的疗效.方法对80例急性附睾-睾丸炎病例随机分为两组,对照组给予传统治疗方法,而治疗组除了传统疗法外,加用皮下环精索封闭治疗.结果治疗组所有患者1～3d内发热、疼痛症状缓解,4～6 d内附睾睾丸肿胀明显减退,97.5%的病例2周内治愈;而对照组40%的患者1～3d内发热、疼痛症状缓解,75%的患者4～6d内附睾睾丸肿胀减退,80%患者2周内治愈,治疗组疗效优于对照组.结论皮下环精索封闭疗法可以迅速缓解临床症状,缩短病程,提高治愈率,是治疗急性附睾-睾丸炎的有效方法.     

Recycling and EH domain proteins at the synapse

In neurons, a network of endocytic proteins accomplishes highly regulated processes such as synaptic vesicle cycling and the timely internalization of intracellular signaling molecules. In this review, we discuss recent advances on molecular networks created through interactions between proteins bearing the Eps15 homology (EH) domain and partner proteins containing the Asn–Pro–Phe (NPF) motif, which participate in important aspects of neuronal function as the synaptic vesicle cycle, the internalization of nerve growth factor (NGF), the determination of neuronal cell fate, the development of synapses and the trafficking of postsynaptic receptors. We discuss novel functional findings on the role of intersectin and synaptojanin and then we focus on the features of an emerging family of EH domain proteins termed EHDs (EH domain proteins), which are important for endocytic recycling of membrane proteins.     

Intubating conditions and onset of neuromuscular block of rocuronium (Org 9426); a comparison with suxamethonium

The intubating conditions and neuromuscular blocking profile following 600 micrograms.kg-1 rocuronium (Org 9426) have been investigated in patients under various experimental conditions. They were compared with conditions following 1.5 mg.kg-1 suxamethonium, preceded by a precurarising dose (10 mg) of gallamine, and with those in a control group in the absence of a muscle relaxant. Rocuronium produced good to excellent intubating conditions at 60 as well as at 90 s after administration, even though there was only a partial blockade of the adductor pollicis muscle. Intubating conditions following suxamethonium were comparable with those after rocuronium. Half of the control patients could be intubated. The clinical duration and the recovery time of 600 micrograms.kg-1 of rocuronium were 24(4) and 9(3) min (mean(s.d.)), respectively. Rocuronium may have a major advantage over existing non-depolarising muscle relaxants due to the early presence of excellent intubating conditions. The results indicate that rocuronium may replace suxamethonium in procedures in which rapid sequence induction is required.     

Ethanol Feeding Causes Inactivation of Both State 1 and State 2 Rat Hepatic Asialoglycoprotein Receptors

Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of ˜50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function , Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs.     

Pharmacological evaluation of natural product analogues. I. Preliminary pharmacological evaluation of O-methylgortschakoine and O-methylpetaline

The synthesis of O-methylgortschakoine and O-methylpetaline was achieved through an unambiguous route. Pharmacological testing of O-methylgortschakoine in comparison to papaverine and 7,8-dimethoxy-N-methyltetrahydroisoquinoline, indicated that it possesses hypotensive, neuromuscular blocking and smooth muscle relaxant activities. 7,8-Dimethoxy-N-methyltetrahydroisoquinoline showed only nonspecific smooth muscle relaxation in our testing system. The 1-(p-methoxybenzyl)-substituent of O-methylgortschakoine appears to be required for this hypotensive and neuromuscular blocking effect. The quaternary analogue O-melthylpetaline was found to possess a more potent neuromuscular blocking activity.     

Heart failure: Effects of beta receptor antagonists on left ventricular function in patients with clinical evidence of heart failure after myocardial infarction. A double-blind comparison of metoprolol and xamoterol Echocardiographic results from the Metoprolol and Xamoterol Infarction Study (MEXIS)

Two hundred and ten patients with clinical evidence of heartfailure, developing after an acute myocardial infarction, wererandomized to treatment with the ß₁ antagonist metoprolol50–100mg b.i.d. (n=106) or the ß₁ partial agonistxamoterol 100–200 mg bid. (n=104). Left ventricular systolicand diastolic function were assessed with echocardiography andtransmitral Doppler cardiography before and after 3 and 12 monthsof double-blind treatment. E-point septal separation and percent left ventricular fractional shortening were used as indicesof systolic function. The ratio between peak early and latemitral diastolic flow (E/A ratio) and isovolumic relaxationtime were used as indices of diastolic function. In the xamoterol group, there was a deterioration in E-pointseptal separation (P<0·05). A difference between thetreatment groups was present both at 3 months (E-point septalseparation 11·4 vs 13·0 mm, P<0·0l,fractional short ening 271 vs 252%, P<005) and 12 months(E-point septal separation Ill vs 13·2 mm, P<0·05fractional shortening 26·9 vs 25·0%, P<0·05).E/A ratio increased in the metoprolol group (P<0·05)but not in the xamoterol group. At 3 months there was a significantdifference (0·85 vs 0·67, P<0·005 betweenthe groups but not at 12 months. In comparison with the ß₁-receptor antagonist metoprolol,the ß₁ partial agonist xamoterol impaired left ventricularsystolic function in patients with clinical evidence of heartfailure after an acute myocardial infarction.     

Selective modification at the N-terminal region of human growth hormone that shows antagonistic activity

A new analogue of recombinant human growth hormone (hGH), hGH des(1–6,14) was expressed in Escherichia coli, refolded and purified to homogeneity. The mutation decreased the hormone's ability to bind lactogenic and somatogenic receptors through its site 1, and almost completely abolished its ability to bind these receptors through site 2, as evidenced by both binding and gel-filtration experiments. More specifically, the binding to prolactin receptors (PRLRs) from various species or their soluble recombinant extracellular domains (ECDs) was decreased 1.5–4-fold, whereas the binding to hGH receptor (hGHR) was decreased 10–85-fold. These changes caused an almost total loss of hormone agonistic activity in several in vitro bioassays and subsequently, the hGH des(1–6,14) analogue acquired antagonistic properties. This antagonistic activity was dependent upon modification of site 1. In those cases in which the binding was reduced only slightly, e.g. binding to rabbit PRLRs, hGH des(1–6,14) acted as a strong antagonist, whereas in others in which the binding of site 1 was reduced to a higher degree, such as other PRLRs and, in particular, hGHR, the antagonistic activity was correspondingly weaker. Circular dichroism spectra of the analogue suggested that these changes do not result from a decrease in overall -helix content, but rather from minor local structural modifications at the N-terminus.     

Differential effect of pancuronium at the adductor pollicis, the first dorsal interosseous and the hypothenar muscles. An electromyographic and mechanomyographic dose-response study

Cumulative dose-response curves were constructed from evoked compound electromyographic (EMG) recordings in man to compare the sensitivity to pancuronium of the adductor pollicis, the hypothenar and the first dorsal interosseous muscles. Also, the EMG and mechanomyography-based sensitivity of the adductor pollicis muscle were compared. The EMG and the mechanomyogram were evaluated in random sequence in each of 21 adult thiopental, fentanyl and diazepam anesthetized patients. The EMG-based ED50 were 36-38 micrograms.kg-1 with no differences between muscles. The EMG-based ED90 of the adductor pollicis and the hypothenar muscles were 62-65 micrograms.kg-1 compared to the 60 micrograms.kg-1 of the first dorsal interosseous muscle (P < 0.05). ED50 (34 micrograms.kg-1), and ED90 (56 micrograms.kg-1) obtained from the adductor pollicis mechanomyogram were significantly lower than those based on the EMG (P < 0.05). It is concluded that differences in sensitivity to pancuronium exist between the three muscles when evaluated from the EMG, and that the apparent sensitivity of a given muscle to a muscle relaxant may depend upon whether the response is evaluated using EMG or mechanomyography.     

肝钳与肝门阻断的肝损害及其防治的实验研究

本实验观察不同阻断时刻肝钳与肝门阻断的肝损害以及预防性应用抗氧化剂的缓解作用。结果表明：（１）ＳＧＰＴ、ＴＢ在肝钳组的变化比肝门阻断组表现得更为一过性。而肝门阻断给药组的改变要比非给药组的轻微且恢复得快。（２）肝门阻断时，ＭＤＡ含量显著升高，机体的Ｔ－ＡＯＣ和ＳＯＤ下降。而给药组可明显减轻上述改变。（３）随着肝门阻断时间的延长，肝组织损害也相应加重，抗氧化剂的给予缓解了肝缺血和再灌注造成的组织损害。肝钳组由于健肝血供未受干扰，因此，不同阻断时刻肝组织学形态与对照组相似无甚改变。结论：（１）肝钳较肝门阻断的肝损害轻，且实用安全。（２）肝门阻断预防性使用抗氧化剂，可明显减轻肝缺血再灌注损害。（３）肝门阻断时经门静脉较外周静脉输注抗氧化剂，其保护作用更直接、明显