Variation in the ability of neuroleptics to block the inhibitory influence of dopaminergic neurons on the activity of cells in the rat prefrontal cortex

The stimulation of the ventro-medial mesencephalic tegmentum (VMT) induces an inhibition of the spontaneous activity of prefrontal cortical cells and blocks the excitatory responses evoked by the stimulation of the medio-dorsal nucleus of the thalamus (MD). This effect is mediated by the activation of the mesocortical dopaminergic (DA) system. In the present study, the influence of the systemic administration of several neuroleptics on the inhibition of prefrontal cortical cells induced by VMT stimulation has been analyzed in ketamine anaesthetised rats. The acute IP administration of fluphenazine (2 mg/kg), spiroperidol (2 mg/kg) or (+/-)sulpiride (100 mg/kg) reversed the inhibitory responses. Moreover, the number of cortical cells inhibited by VMT stimulation was considerably decreased after these treatments. Surprisingly, neither haloperidol at any dose used (0.1 to 0.5 mg/kg IV or 0.5 to 5 mg/kg IP) nor levomepromazine (25 mg/kg IP) nor the long acting neuroleptic, pipotiazine palmitic ester (32 mg/kg SC) blocked the inhibitory effect of VMT stimulation and in fact they lengthened the duration of the inhibition. Finally, the inhibition of MD evoked spikes in prefrontal cortical cells produced by VMT stimulation was no longer observed after sulpiride but persisted after haloperidol administration. Our findings confirm that the mesocortico-prefrontal DA neurons exert an inhibitory influence on target cells but they reveal differences in the efficacy of neuroleptics in blocking this effect.     

用自组织理论浅析医学诊疗思维的差异

自组织理论不仅证实了物质自我运动、自我发展的科学原理,而且为我们认识研究各种事物的演化、发展提供了具有普遍意义的新思路和新方法。熟谙生命系统的自组织性,恰当运用医学思维模式,对于开拓诊疗思维、提高诊疗效果会提供有益尝试和多元选择。     

Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy

BACKGROUND: Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. OBJECTIVE: The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. METHODS: Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. RESULTS: IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. CONCLUSION: While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid concept.     

Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.     

善宁治疗顽固性大咯血疗效观察

目的 评价善宁对顽固性大咯血的疗效。方法 将55例传统药物抢救无效或有禁忌的大咯血分为治疗组（善宁）与对照组（立止血组），观察24—72h的止血效果。结果 治疗组总有效率为92％，对照组为70％，两组比较有显著差异p〈0．05（x^2=4．125）。结论 善宁治疗大咯血疗效显著，使用安全，不良反应少，值得临床推广应用。     

正常人与重症肌无力患者胸腺提取液免疫活性比较

用~３Ｈ－ＴｄＲ掺入法观察不同稀释度的正常人与重症肌无力患者胸腺提取液对健康成人外周血淋巴细胞增殖的影响。实验证实了正常儿童的胸腺功能下降（高浓度Ｐ＜０．０２，余浓度Ｐ＞０．０５），成人胸腺无功能（Ｐ＞０．０５）；并且得出增生型重症肌无力胸腺提取液对ＰＨＡ诱导的人外周血淋巴细胞增殖有促进和抑制双向作用。提示重症肌无力患者的胸腺免疫活性与正常人比较有差异。解释并肯定了手术切除胸腺治疗增生型重症肌无力的作用。     

百事特蜂王宝对受抑小鼠免疫功能的影响

为了探讨蜂王宝对免疫功能的影响,用蜂王宝对受抑小鼠进行了淋巴细胞增殖,抗体形成细胞等免疫功能试验。在正常淋巴细胞增殖中,蜂王宝组与正常对照组比较差异非常显著(P<0.01),在PHA诱导的小鼠淋巴细胞增殖中,蜂王宝组与正常对照组比较和蜂王宝+强的松龙组与强的松龙组比较差异也非常显著(P<0.01).蜂王宝+强的松龙组与强的松龙组的脾重比较差异有显著性(P<0.05),结果显示,蜂王宝能显著提高受抑小鼠淋巴细胞增殖能力,而对体液免癌无明显作用。     

多普勒超声心动图食道调搏负荷试验对冠心病左室功能的评价

本文对１９例冠心病患者和１３例健康人进行了经食道心房调搏负荷多普勒超声心动图检查，旨在观察此法对冠心病患者的诊断价值。结果表明：（１）静息状态下多普勒超声心动图各项心功能指标二组之间无显著差异（Ｐ＞０．０５）；（２）在经食道心房调搏试验中左心室收缩指标Ｖｍａｘ、Ｖｍｅａｎ、ＶＴＩ、ＳＶ、ＣＯ等与对照组比较有显著差异（Ｐ＜０．００ｌ），以此几项指标进行二类判别分析，符合率达９３．７５％。结论认为经食道心房调搏负荷多普勒超声心动图是诊断冠心病的一项较敏感、无创易行的方法。     

Suppressive effect of immature erythroid cells on the B-cell proliferation

Immature erythroid cells suppress the proliferative response of preactivated B lymphocytes to lipopolysaccharide. The same effect is observed when recombinant human interleukin-2 or culture medium conditioned by preactivated T or B cells is added to cultured cells. Suppressive nucleate erythroid cells are resistant to leucine methyl ester. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 1, pp. 66–70, January, 1997