高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Non-invasive dynamic assessment of the elasticity of intracranial structures

The dynamics of the speed of transcranial propagation of ultrasonic impulses has been established in humans. The possibility of detecting the changes in mechanical state of intracranial structures by dynamic measurement of the time of transcranial propagation of ultrasonic impulses (TUPT) has been ascertained for 10 healthy persons and 11 patients with different neurological pathology. The cerebrospinal fluid pressure (CSFP) was simultaneously monitored for 4 of the patients. Spontaneous fluctuations in TUPT and the changes caused by jugular veins, inferior vena cava compression, hyperventilation and temporary retention of breathing were detected for all investigated subjects. Spontaneous TUPT changes in the range of 0.25-0.85 x 10(-4) of initial mean value, which are related with cardiac and respiratory cycles, have been found in healthy persons while in patients they ranged from 0.07 x 10(-4) to 4.5 x 10(-4) of mean time. In healthy persons bilateral jugular vein compression leads to a decrease in TUPT by 1.8-3.0 x 10(-4), while the compression of inferior vena cava gives an increase in TUPT by 1.6-2.6 x 10(-4). Changes in TUPT during these maneuvers in neurological patients were found to be of different amplitude and direction. The rise of CSFP by 8.4-20.2 mmHg (mean 12.4 mmHg) was observed in 4 investigated patients during the compression of jugular veins or during the inferior vena cava compression, while the changes in TUPT obtained during each of such maneuvers were of opposite character. The results suggest that dynamic evaluation of acoustic impedance of intracranial system reflects the changes in the mechanical state of brain parenchyma.     

傅立叶变换红外光谱用于不同状态胆囊组织的初步研究

目的:探索正常、炎性和癌变胆囊组织各自特异的傅立叶变换红外光谱(FT-IR)表现。方法:应用FT-IR对7例正常胆囊组织、7例炎性胆囊组织和2例胆囊癌组织标本进行检测,总结与组织状态相关的光谱特征。结果:胆囊正常、炎性和癌组织具有不同的FT-IR光谱表现,1550cm~(-1)处的酰Ⅱ带在癌组织中表现较弱,峰形低平,而在正常组织中则较强,峰形高尖。相叶强度Ⅰ1550与Ⅰ1647的比值在7例正常组织中为0.33,0.48.0.54,0.38,0.41,0.52,0.45,炎性组织中为0.32,0.27,0.34,0.25,0.33,0.28,0.29,2例癌组织分别为0.25和0.28;Ⅰ1080与Ⅰ1550的比值在正常组织中为0.059,0.042,0.077,0.085,0.092,0.100,0.081,炎性组织中为0.046,0.040,0.053,0.053,0.048,0.078,0.100,2例癌组织中为0.110和0.170。正常组织中1453cm~(-1)处的峰值高于1402cm~(-1)处,而在癌组织中则相反。结论:胆囊正常、炎性和癌组织的FT-IR表现不同,FT-IR有望成为胆道疾病临床诊断的一种新手段。     

Neoplastic involvement of the sacroiliac joint: MR and CT features

The radiological findings in five patients with pelvic sort tissue neo plasms directly involving the sacroiliac joint, are described. All patients had Computed Tomography (CT) examinations, two of the patients also having Magnetic Resonance Imaging (MRI). The role of imaging in this uncommon entity is discussed as well as the importance of making this diagnosis, thereby excluding unilateral sacroiliitis. The therapeutic implications of this diagnosis relate to local neural involvement, especially the sciatic nerve, and the fact that involvement of the sacroiliac joint by tumors significantly compromises chances of a successful surgical outcome. The role of MR in this condition is not yet certain, but it may prove to be the method of choice in view of its excellent depiction of skeletal neo plasms.     

654─2在小儿急性脑水肿及中枢性呼吸衰竭中的应用探讨

感染性脑水肿病儿在感染得到有效控制，应用654—2（山莨菪碱）后未再用脱水剂，笔者认为．654—2具有解除脑血管痉挛及微循环障碍的作用。急性脑水肿在脱水剂应用后，用654—2有利于脑水肿液的吸收和回流。目前，治疗小儿捂热综合征（IMS）之细胞内水肿仍没有有效的方法，研究结果表明654—2能改善脑细胞供氧．其还能通过解除呼吸中枢血管痉挛而治疗中枢性呼吸衰竭。     

Synthesis and cytotoxic activity of new alkyl[3-(2-chloroethyl)ureido]benzene derivatives

Several alkyl[3-(2-chloroethyl)ureido] (CEU) benzene derivatives were prepared as potential anticancer agents. These new compounds were readily prepared in good yields by addition of anilines to 2-chloroethylisocyanate. Their cytotoxic activity was evaluated on human breast cancer (MDA-MB-231), human colon adenocarcinoma (LoVo) and mouse lymphocytic leukemia (P388D₁) tumor cell lines. Several new CEUs were significantly more cytotoxic than the nitrogen mustard chlorambucil. The biological activity of these aromatic urea derivatives seems to be related to the nature and position of the alkyl substituents on the aromatic ring. Substitution by branched alkyl groups on position 4 of the aromatic ring led to cytotoxic molecules which are up to 5 times more potent than the standard chlorambucil.     

小儿白血病瘤细胞P—糖蛋白测定方法及应用

本文介绍免疫组化法检测小儿白血病瘤细胞（Ｐ－ｇｐ）。检测３０例小儿白血病细胞膜Ｐ－ｇｐ，观察其原发耐药性。３０例中有８例ｐ－ｇｐ阳性，总阳性率２６．６７％，其中ＡＮＬＬ单项阳性率３３．３３％，ＡＬＬ为２０％。本组病例耐约性最高的是ＣＭＬ，其次是ＡＮＬＬ，ＡＬＬ组最低。同时发现ＭＤＲ阳性者复发率高，ＭＤＲ阴性者复发率低，多因素分析表明ＭＤＥＲ对初诊白血病患者预后及抗癌药物选择有重要意义。目的临床评价ＭＤＲ采用检测ｍｄｒ１ｍＲＮＡ或Ｆ－ｇｐ，本文认为采用简便、快速的免疫组化法检测Ｐ－ｇｐ在临床上具有较大的实用价值。     

Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease

BACKGROUND: Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease. OBJECTIVE: To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared. METHODS: We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years). RESULTS: Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls. CONCLUSION: The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.     

ERK信号传导通路调控乙醛刺激的肝星状细胞Na+/Ca2+泵mRNA表达的研究

目的 :探讨Erk信号传导通路调控乙醛刺激的肝星状细胞 (HSC)Na /Ca2 泵mRNA表达的影响。方法 :用链霉蛋白酶和胶原酶原位灌流 ,Metrizamide密度梯度离心分离大鼠肝星状细胞 ,采用RT PCR测定PD980 5 9阻断乙醛激活的肝星状细胞Erk活性后Na /Ca2 泵mRNA表达。结果 :乙醛刺激后 ,HSC后明显促进Na /Ca2 泵mRNA表达 (P<0 0 1) ,不同剂量PD980 5 9对肝星状细胞Na /Ca2 泵mRNA表达的影响无统计学意义。结论 :Erk信号传导通路可能对乙醛刺激的肝星状细胞激活状态的启动无明显影响     

New players in old amyloid precursor protein-processing pathways

The amyloid precursor protein (APP) gives rise to beta-amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease (AD) patients. The generation of beta-amyloid peptides requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by neurons and increased BACE1 protein concentrations and enzymatic activities have been reported in the brains of AD patients. However, there is accumulating evidence that, in addition to neurons, reactive astrocytes are capable of expressing BACE1 and, therefore, may contribute to beta-amyloid plaque formation. This suggests that conditions accompanied by chronic astrocyte activation may contribute to developing AD. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG) generation. This led to the hypothesis that classical and novel protein kinase Cs (PKCs), which are activated by DAG/PEs, regulate APP processing. However, in addition to PKCs, there are other DAG/PE receptors present in neurons which may participate in the modulation of APP processing. Munc13-1, a presynaptic protein with an essential role in synaptic vesicle priming, represents such an alternative target of the DAG second messenger pathway. Using Munc13-1 knock-out mice and human neuroblastoma cells transfected with wild-type and mutant Munc13-1 constructs it was demonstrated that Munc13-1 acts independently of and in parallel with PKC to modulate APP metabolism. Therefore, agonists specific for the Munc13-1 C1-domain or small molecules mimicking the function of the endogenous Munc13-1 activator RIM1 may prove useful to shift APP processing towards the non-amyloidogenic pathway.