Effects of synthetic sphingosine-1-phosphate analogs on arachidonic acid metabolism and cell death

Sphingolipid metabolites such as sphingosine regulate cell functions including cell death and arachidonic acid (AA) metabolism. D-erythro-C18-Sphingosine-1-phosphate (D-e-S1P), a sphingolipid metabolite, acts as an intracellular messenger in addition to being an endogenous ligand of some cell surface receptors. The development of S1P analogs may be useful for studying and/or regulating S1P-mediated cellular responses. In the present study, we found that several synthetic S1P analogs at pharmacological concentrations stimulated AA metabolism and cell death in PC12 cells. D-erythro-N,O,O-Trimethyl-C18-S1P (D-e-TM-S1P), L-threo-O,O-dimethyl-C18-S1P (L-t-DM-S1P) and L-threo-O,O-dimethyl-3O-benzyl-C18-S1P (L-t-DMBn-S1P) at 100 microM stimulated [(3)H]AA release from the prelabeled PC12 cells. L-t-DMBn-S1P at 20 microM increased prostanoid formation in PC12 cells. L-t-DMBn-S1P-induced AA release was inhibited by D-e-sphingosine, but not by the tested PLA(2) inhibitors. L-t-DMBn-S1P did not stimulate the activity of cytosolic phospholipase A(2alpha) (cPLA(2alpha)) in vitro and the translocation of cPLA(2alpha) in the cells, and caused AA release from the cells lacking cPLA(2alpha). These findings suggest that L-t-DMBn-S1P stimulated AA release in a cPLA(2alpha)-independent manner. In contrast, D-e-S1P and D-erythro-N-monomethyl-C18-S1P caused cell death without AA release in PC12 cells, and the effects of D-e-TM-S1P, L-t-DM-S1P and L-t-DMBn-S1P on cell death were limited. Synthetic S1P analogs may be useful tools for studying AA metabolism and cell death in cells.     

糖尿病尿LN和Ⅳ-C与中医证型的关系

目的探讨糖尿病患者层黏连蛋白(LN)和尿中Ⅳ型胶原(IV-C)与阴虚燥热、气阴亏虚两种证型之间的关系。方法以我院收治的180例糖尿病患者及30例正常体检者为研究对象,应用放免法测定尿LN及IV-C,并用放射免疫比浊法CBA检测mAlb水平。结果 (1)气阴亏虚型的糖尿病患者的尿LN、IV-C、mAlb较阴虚燥热型有显著升高(P<0.01)。(2)糖尿病阴虚燥热型与气阴亏虚型尿LN与mAlb呈正相关,r=0.230,P<0.01;尿IV-C与mAlb呈正相关,r=0.057,P<0.01;尿IV-C与尿LN呈正相关,r=0.624,P<0.01。结论糖尿病中医证型中尿IV-C、LN存在差异,尿IV-C、LN水平可能是DM患者出现不同中医证型的客观指标之一。     

高效液相色谱法同时测定血清中几种脂溶性维生素

目的:采用高效液相色谱(HPLC)技术同时测定维生素A(VA)、维生素E(VE)、β-胡萝卜素(β-C)和番茄红素(Ly)。方法:HPLC柱:AlltechODS5μm(250mm×4.6mmi.d.);流动相:甲醇∶乙酸乙酯∶正己烷=7∶2∶2(v∶v∶v);检测波长:VA,VE,β-C和Ly的检测波长分别为325nm、292nm、450nm和472nm(波长编程,自动转换)。灵敏度:0.002AUFS;流速:1.0ml/min。结果:VA,VE,Ly和β-C的保留时间分别是4.5,6.5,9.4和13.4min,4种成分峰独立完整,无干扰峰,峰形和分离效果良好,并在15min之内可完成分析测定。结论:本研究首次建立了一次同时测定VA、VE、β-C和Ly的方法,既节省时间和试剂,又快速、准确。     

Molecular targets of dietary agents for prevention and therapy of cancer

While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.     

Integration in descending motor pathways controlling the forelimb in the cat

Summary Recording was made in the C3-C4 segments from cell bodies of propriospinal neurones identified by their antidromic activation from more caudal segments. Monosynaptic excitatory effects from descending motor pathways and primary afferents were investigated by electrical stimulation of higher motor centres and peripheral nerves in the forelimb and neck.The cell bodies were located mainly laterally in Rexed's layer VII. Threshold mapping for single axons showed that they descend in the lateroventral part of the lateral funicle. Antidromic stimulation at different spinal cord levels showed that some neurones terminated in the forelimb segments, others in the thoracic cord or in the lumbar segments. Terminal slowing of the conduction velocity suggested axonal branching over some segments.Monosynaptic EPSPs were evoked in the neurones by stimulation of the contralateral pyramid, red nucleus and dorsal tegmentum-superior colliculus. It is concluded that corticospinal, rubrospinal and tectospinal fibres project directly to both short and long propriospinal neurones. There was marked frequency potentiation in tectospinal synapses. Convergence from two descending tracts was common and in half of the tested cells all three tracts contributed monosynaptic excitation. Experiments with collision of descending volleys and antidromic volleys from the brachial segments demonstrated that the corticospinal and rubrospinal monosynaptic projection to the propriospinal neurones is by collaterals from fibres continuing to the forelimb segments.Stimulation of cervical primary afferents in the dorsal column gave monosynaptic EPSPs in somewhat less than half of the tested propriospinal neurones. The further analysis with stimulation of forelimb nerves and C2-C3 dorsal rami showed that monosynaptic EPSPs may be evoked from low threshold cutaneous and group I muscle afferents in the forelimb and from C2-C3 neck afferents entering close to the spinal ganglia, possibly from joint receptors. Convergence from cervical afferents and at least two of the above descending tracts was common.It is postulated that the propriospinal neurones previously indirectly defined by their action on motoneurones as relaying disynaptic excitation from higher motor centres to forelimb motoneurones (Illert et al., 1977) belong to those neurones of the C3-C4 propriospinal systems which terminate in the cervical enlargement. The function of the neurones projecting beyond the upper thoracic segments is discussed.Supported by the Deutsche ForschungsgemeinschaftIBRO/UNESCO Fellow     

新疆维吾尔族人群HLA多态性血清学的研究

作者报告维吾尔族人群ＨＬＡ多态性。维吾尔族人群ＨＬＡ抗原基因频率较高的有：Ａｌ、Ａ３、Ａ２６、Ｂ７、Ｂ８、Ｂ１４和ＤＲＩ。根据第十一届国际组织相容性会议（１１ｔｈＩＨＷＣ）数据分析中心由ＨＬＡ－Ａ和Ｂ座位上抗原的基因频率，按不加权的对群体聚类法计算绘制出人种的亲缘关系树系图显示：维吾尔族人群聚类进高加索人种中，但维吾尔族又具有蒙古人种特有的ＢＷ４６和ＢＷ５４。所以我们认为维吾尔族ＨＬＡ多态性介于蒙古人种和高加索人种之间。     

(±)-13β,17α-二乙基-17β-羟基甾烷骈[3,2-C]吡唑及[2,3-C]呋咱的合成

以(±)-13β,17α-二乙基-17β-羟基-5α-甾烷-3-酮(Ⅱ)为原料,经甲酰化、缩合反应合成了(±)-13β,17α,-二乙基-17β-羟基-5α-甾烷骈[3,2-C]吡唑(Ⅴ);又将甲酰化反应所得羟次甲基化合物(Ⅳ)依次转变成单肟(Ⅵ)、双肟(Ⅶ)、再坏合成(±)-13β,17α-二乙基-5α-甾烷骈[2,3-C]呋咱(Ⅷ)。 采用类似的反应,从(Ⅱ)及(Ⅳ)的5β-异构体(Ⅲ)和(Ⅸ)分别合成了(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[3,2-C]吡唑(Ⅹ)与(±)-13β,17α-二乙基-17β-羟基-5β-甾烷骈[2,3-C)呋咱(ⅩⅢ)。     

芪术颗粒对大鼠白蛋白肝纤维化模型的预防作用

用人血白蛋白复制大鼠肝纤维化模型，观察了芪术颗粒对该模型的预防作用。血清生化检查及肝组织HE、Nasson染色观察和图像分析表明，芪术颗粒能降低实验大鼠血清PⅢP、Ⅳ-C含量，并能减轻肝纤维化程度。