Dynamic observations on NK cell activity and IL-2 and IFNγ productionin vitro in patients on maintenance hemodialysis

Summary In order to study the immune function of patients on maintenance hemodialysis (MHD), we assayed NK cell cytotoxicity against K⁵⁶² targets in 40 patients on MHD, and the production of IL-2 and IFN in peripheral blood mononuclear cells (PBMC) after PHA stimulation, in contrast to those in normal controls. The results showed that NK cell activity and IL-2 and IFN levels were markedly lower in the patients than in the controls. Afeter a single dialysis, NK cell activity as well as IL-2 and IFN levels were elevated to different extent. But there was no significant change in patients after long-term dialysis. There was a positive correlation between the NK cell activity and IL-2 and IFN activity in the controls, but no such correlation was found in the patients on MHD. There was a positive correlation between the NK cell activity and IL-2 activity in patients after dialysis, suggesting that immune function were impaired in the patients on MHD, with a decline in the activity of NK cell and IL-2 and IFN, and a disorder of immune regulation cycle. These abnormal immune impairments in the patients could be partly corrected by hemodialysis. However, long-term hemodialysis is not much helpful in the improvement of patient’s immune function.     

Biological properties of interleukin-12 and its therapeutic use in persistent hepatitis B virus and hepatitis C virus infection

Summary. Interleukin (IL)-12 is a pleiotropic cytokine produced by antigen-presenting cells in response to diverse stimuli. IL-12 is a key molecule in the regulation of host's immune responses. In particular, IL-12 influences the balance between the T-helper cells type 1 (TH₁) and type 2 (TH₂); it modulates macrophage responses through the control of interferon-gamma synthesis by TH₁ cells; and, suppresses IgE class antibody production (has a suppressive effect on allergic reactions) and promotes a shift in the IgG subclasses. IL-12 enhances resistance to several infectious diseases, is a powerful antitumor agent in vivo , and acts as a vaccine adjuvant. The biological properties of IL-12 point to the potential therapeutic use in persistent hepatitis B virus and hepatitis C virus infection.     

胆源性感染性休克兔血栓素、前列环素与血小板聚集率的变化

动态观察胆总管急性完全性梗阻并感染、继发休克兔的血浆血栓素(TXA_2)和前列环素(PGI_2)的稳定代谢产物 TXB_2和6-keto-PGF_(1α)含量及血小板聚集率的变化。结果,血浆 TXB_2呈进行性升高,20h 后(休克时)呈下降趋势,血浆6-keto-PGF_(1α)6h 升高,随后回降;血小板聚集率呈进行性下降。提示血栓素和前列环素、血小板聚集率的变化在重症急性胆管炎、胆源性感染性休克发病过程中起重要病理生理作用,与病情和预后转归有重要联系。     

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

1 Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia.
2 Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N -demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms.
3 After a single, oral 30  mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes.
4 The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL C _max 59  nmol l⁻¹ and AUC (0, t h) 144  nmol l⁻¹h, mean MDL C _max 183  nmol l⁻¹ and AUC 2627  nmol l⁻¹h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL C _max 356  nmol l⁻¹ and AUC 10512  nmol l⁻¹h, MDL concentrations below limit of quantitation).
5 We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.     

Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

医院用血液制品HCV污染情况的调查

目的调查医院治疗用血液制品ＨＣＶ污染情况．方法临床治疗所用的血液制品，在输完后留容器之残液备检．采用酶标免疫法（ＥＬＩＳＡ）检测．对ＥＬＩＳＡ检测之阳性标本及在阴性标本中随机抽取９份，采用逆转录双ＰＣＲ方法检测ＨＣＶ＿ＲＮＡ．结果血浆白蛋白抗＿ＨＣＶ阳性率４５８％，新鲜血浆阳性率２６％．两种方法检测同一标本，ＥＬＩＳＡ检测阳性的血液制品中，用ＰＣＲ证实，并非都有病毒复制；而在ＥＬＩＳＡ检测的阴性标本中，仍旧有较高的ＰＣＲ阳性检出．结论血液制品存在着ＨＣＶ污染，抗＿ＨＣＶ对于ＨＣＶ感染的诊断价值很高．检测血液制品中的抗＿ＨＣＶ，合理使用血液成份，可防止ＨＣＶ在医院内传播．     

三硝基甲苯的代谢物—2-氨基-4,6-二硝基甲苯和2,4-二氨基-6-硝基甲苯的合成

本文报告了2,4,6-三硝基甲苯(TNT)的代谢物,2-氨基-4,6-二硝基甲苯2和2,4-二氨基-6-硝基甲苯3的合成。以邻甲基苯甲酸为原料,经硝化(HNO_3-H_2SO_4)和Schmidt反应(NaN_3-H_2SO_4)得到2,用NaHS还原TNT的方法合成化合物3。