浮萍的化学成分研究△

从中药浮萍的正品紫萍的乙醇提取物中分离出4个黄酮化合物,经理化常数和光谱鉴定其结构,分别为芹菜素(apigenin)、木犀草素(luteolin)、芹菜素-7-O-葡萄糖苷(apegenin-7-O-glucoside)和水犀草素-7-O-葡萄苷(leuteolin-7-O-glucoside),它们是紫萍中的主要化学成分。     

Influence of early posttraumatic hypothermia therapy on local cerebral blood flow and glucose metabolism after fluid-percussion brain injury

OBJECT: Using autoradiographic image averaging, the authors recently described prominent foci of marked glucose metabolism-greater-than-blood-flow uncoupling in the acutely traumatized rat brain. Because hypothermia is known to ameliorate injury in this and other injury models, the authors designed the present study to assess the effects of posttraumatic therapeutic hypothermia on the local cerebral metabolic rate of glucose (LCMRglu) and local cerebral blood flow (LCBF) following moderate parasagittal fluid-percussion head injury (FPI) in rats. METHODS: Either cranial hypothermia (30 degrees C) or normothermia (37 degrees C) was induced for 3 hours in matched groups of rats immediately after FPI; LCMRglu and LCBF were assessed 3 hours after concluding these temperature manipulations. In rats subjected to FPI, regardless of whether normothermia or hypothermia ensued, LCBF was reduced relative to the sham-injury groups. In addition, when FPI was followed by hypothermia (FPI-30 degrees C group), the subsequent LCBF was significantly lower (35-38% on average) than in FPI-37 degrees C rats. Statistical mapping of LCBF difference imaging data revealed confluent cortical and subcortical zones of significantly reduced LCBF (largely ipsilateral to the prior injury) in FPI-30 degrees C rats relative to the FPI-37 degrees C group. Local glucose utilization was reduced in both hemispheres of FPI-37 degrees C rats relative to the sham-injury group and was lower in the right (traumatized) hemisphere than in the left. However, LCMRglu values were largely unaffected by temperature manipulation in either the FPI or sham-injury groups. The LCMRglu/LCBF ratio was nearly doubled in FPI-30 degrees C rats relative to the FPI-37 degrees C group, in a diffuse and bihemispheric fashion. Linear regression analysis comparing LCMRglu and LCBF revealed that the FPI-37 degrees C and FPI-30 degrees C data sets were completely nonoverlapping, whereas the two sham-injury data sets were intermixed. CONCLUSIONS: Despite its proven neuroprotective efficacy, early posttraumatic hypothermia (30 degrees C for 3 hours) nonetheless induces a moderate decline in cerebral perfusion without the (anticipated) improvement in cerebral glucose utilization, so that a state of mild metabolism-greater-than-blood-flow dissociation is perpetuated.     

Recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor as an anticoagulant in venovenous extracorporeal circulation in rabbits

Investigations were performed to characterize a recombinant Kunitz protease inhibitory domain of the amyloid beta-protein precursor (rKPI) as anticoagulants. After a single intravenous infusion of wild type rKPI into dogs, its elimination fit a two compartment model with a t1/2alpha and t1/2beta of 5 and 77 min, respectively. Further investigations determined if a variant form of rKPI with 178-fold more potent anti-factor Xa activity (rKPI-DD135, Ki = 0.9 nM) could serve as an anticoagulant in a rabbit model of extracorporeal circulation using a venovenous shunt. A prospective investigation was initiated to compare standard heparin (n = 8) at 400 U/kg with different infusion concentrations of rKPI-DD135. After a single intravenous infusion of 1.89 mg/kg of rKPI-DD135 followed by a constant infusion at 0.003 (n = 3), 0.03 (n = 7), or 0.3 (n = 5) mg/kg/min, the anti-factor Xa activity of the animals' plasma rapidly reaches a steady state for the two lower infusion concentrations of the agent. All infusions of rKPI-DD135 prolong the activated clotting time with less variation than that seen with heparin administration. rKPI-DD135 anticoagulation does not prevent a drop in the platelet counts. Fibrinogen levels decrease only slightly when the circuit is anticoagulated with rKPI-DD135. rKPI-DD135 markedly prolongs the APTT, has little effect on the PT, and reduces plasma prekallikrein and plasminogen activation. The 0.3 mg/kg/min infusion concentration of rKPI-DD135 results in reduced deposition of 111Indium-labeled platelets on the circuit when compared to heparin. Last, after a steady state level is achieved, 60% of the plasma anti-factor Xa activity of rKPI-DD135 is eliminated within 60 min after stopping the infusion. These data show the rKPI-DD135 can provide single agent anticoagulation in a rabbit extracorporeal circuit. Development of short acting factor Xa inhibitors may be useful anticoagulants for cardiopulmonary bypass.     

Level of sustained entorhinal activity at study correlates with subsequent cued-recall performance: a functional magnetic resonance imaging study with high acquisition rate

Functional magnetic resonance imaging (fMRI) with high acquisition rate was performed during the intentional memorizing of words to specify which medial temporal lobe structure is important in determining what words are subsequently remembered in a cued-recall test and to characterize the time course of activation in that structure. Functional images of six healthy young subjects were analyzed by two subject- and voxel-wise statistics: First, to identify brain areas transiently engaged in encoding of words, brain activity during memorizing visually presented words and watching a fixation cross was compared by a Kolmogorov-Smirnov statistic (KS-test). Second, to identify brain areas whose activity correlates with memory encoding success, a Kendall's correlation was calculated between signal intensity at study and performance in a subsequent cued-recall test. Averaged signal intensities were plotted as a function of time to depict the time course of brain activity detected by both statistical tests. The level of slowly modulated, sustained activity in Brodmann area 28 (entorhinal cortex) did not respond transiently as study words appeared, but did correlate positively with subsequent test performance. More left than right activity in Brodmann area 45 (dorso-lateral prefrontal cortex) and bilateral activity in Brodmann area 44 (premotor cortex) exhibited transient hemodynamic responses that did not show any relation to subsequent memory performance. Thus, the study identified a novel pattern of slowly modulated brain activity in human entorhinal cortex that may represent a declarative memory encoding state whose level predicts whether experiences will be remembered or forgotten.     

Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a

PURPOSE: We have characterized the androgen receptor (AR) in a new human prostate cancer cell line, MDA PCa 2a, that has recently been established from a bone metastasis of a patient whose cancer exhibited androgen-independent growth. MATERIALS AND METHODS: Androgen responsiveness of these cells was assessed by measuring the effect of DHT and R1881 on cell growth and PSA secretion. Scatchard analysis was used to characterize the affinity and abundance of AR protein. Using a PCR based strategy, genomic DNA of the entire coding region of AR gene was sequenced to identify possible mutations. RESULTS: These cells express abundant AR (Nmax = 685 +/- 149 fmol./mg. protein), but the AR binding affinity (Kd) for DHT is only 25 nM, approximately 50-fold lower affinity than the mutated AR in LNCaP prostate cancer cells (Kd = 0.5 nM) or the wildtype AR in MCF-7 breast cancer cells (Kd = 0.4 nM). Two mutations, L701H and T877A, were identified in the ligand binding domain of the AR gene. Compared with LNCaP cells, the new cell line is significantly less responsive to DHT and R1881 as well as to other androgens such as testosterone, androstenedione, and DHEA. Similar to LNCaP cells, the ligand specificity of the AR in MDA PCa 2a cells appears to be relaxed and non-androgens such as progesterone and estradiol act as agonists although with less potency than in LNCaP cells. Interestingly, in the absence of androgens, the new cell line expresses 15-fold higher baseline levels of PSA than LNCaP. CONCLUSIONS: Two mutations were identified in the AR gene of the MDA PCa 2a cell line that are likely responsible for the decreased androgen sensitivity and altered ligand specificity observed in these cells. Thus, this new cell line with partial androgen responsiveness and PSA expression can serve as a functionally relevant model system of bone metastatic prostate cancer, and can be used to investigate the role of AR mutations in prostate cancer and its progression to androgen independence.     

CeReS-18 inhibits growth and induces apoptosis in human prostatic cancer cells

BACKGROUND: Polypeptide growth factors are positive and negative regulators of prostatic growth and function, and many positive regulators of growth in the prostate have been extensively studied. However, very few inhibitors of prostate cell proliferation have been identified. We have isolated a unique 18-kDa sialoglycopeptide (CeReS-18) which inhibits cell proliferation of three separate lines of human prostate cancer cells, as well as inducing cellular cytotoxicity via an apoptotic pathway unrelated to the Bcl-2 family of proteins. METHODS: Cell cycle inhibition was analyzed by direct cell counts with a Coulter (Miami, FL) cell counter. Apoptotic cells were analyzed by electron microscopy, annexin V-fluorescein isothiocyanate (FITC) staining, fluorescence microscopy, and propidium iodide uptake measured with a fluorescence-activated cell sorter. Expression of the proteins of the Bcl-2 family was detected by Western blot analysis. RESULTS: We found that CeReS-18 inhibits cell proliferation of androgen-responsive, LNCaP.FGC human prostate cancer cells, as well as of androgen-nonresponsive DU-145 and PC3 human prostate cancer cells. Furthermore a, fivefold increase over the inhibitory concentration of CeReS-18 elicited a cytotoxic response by all three cell lines. We thus characterized the cytotoxic mechanism as apoptotic in nature, and we measured the expression of several members of the Bcl-2 family in PC3 cells upon treatment with CeReS-18. CONCLUSIONS: The data indicate that CeReS-18 is a potent inhibitor of cellular progression through the cell cycle by both androgen-responsive and androgen-nonresponsive human prostate cancer cells. In addition, treatment of both types of cells with increased concentrations of CeReS-18 induces cellular cytotoxicity, characterized as apoptosis.     

内毒素休克大鼠组织生物喋呤及其合成限速酶基因表达的改变

目的 了解内毒素休克时重要器官生物喋呤及其合成限速酶基因表达的改变和病理生理意义。方法 采用大鼠内毒素休克模型,检测肝,肾,肠等组织生物喋呤含量,三磷酸鸟苷环水解酶Ｉ（ＧＴＰ－ＣＨＩ）ｍＲＮＡ表达及器官功能指标等。并观察内毒素拮抗剂－重组杀菌／通透性增加蛋白（ｒＢＰＩ２１）的防治效果。结果 内毒素休克动物肝,肾,肠等组织生物喋呤含量明显增多,伤后８小时升高幅度尤为显著（Ｐ〈０．０５,Ｐ〈０．０１０     

胃肠道癌手术与门静脉单细胞转移的相关性研究

目的 进一步了解在胃癌、大肠癌的根治过程中,手术对单细胞转移的影响。方法 １７２例２分２组,阳性受检组１１１例,先结扎肿瘤区引渡以血和的阴性对照组６１例。开腹探后将导管置入门静脉抽取血标本,抗上皮细胞膜克隆抗体为探针,ＡＢＣ免疫组化法检测门静脉癌细胞。结果 阳性受检组１１１例患者中有７２例发现肿瘤细胞、阳性率为６４．９％,有性对照组的６１例仅发现１３例,阳性率为２１．３％,两组且间差异有显著性,     

5-氟尿嘧啶在胰十二指肠切除术患者血液和胰液中的动态分布

探讨５－氟尿嘧啶能否通过胰十二指肠切除术后的残留胰腺组织进入胰液中,并达有效的治疗浓度,为胰腺为临床合理化疗提供理论依据。方法通过观察胰十二指肠切除术患者胰快速推注５－氟尿嘧啶后血液和胰液中药物动态分布及相关性,术后静脉一次性快速推注５－氟尿嘧啶１．０ｇ／ｍ＾２,在给药前后按设计时间点分别采集静脉血和胰液,采用高效液相色谱法测定血浆和胰液５－氟尿嘧啶药物浓度,应用ＰＣＮＯＮＬＩＮ程序程序计算共动态