射干的化学成分研究(Ⅰ)

从射干Ｂｅｌａｍｃａｎｄａｃｈｉｎｅｎｓｉｓ根茎的乙醇提取氯仿溶解部分分得９个已知化合物。经理化常数和光谱分析确定为野鸢尾黄素，白射干素，次野鸢尾黄素，３－豆甾烷醇，茶叶花宁，鸢尾甙元，β－谷甾醇（Ⅶ），３＇，４＇，５，７－四羟基－８－甲氧基－异黄酮和八聚异戊二烯类化合物。     

An isorhapontigenin tetramer and a novel stilbene dimer from Gnetum hainanense

The first isorhapontigenin tetramer, gnetuhainin R (1) and a novel dimeric stilbene, gnetuhainin S (2) were isolated from the lianas of Gnetum hainanense. Their structures were elucidated on the basis of spectroscopic and chemical evidence, especially 2D NMR analysis. The structure of 2 was further supported by X-ray crystallographic analysis. The anti-inflammatory activity of 1 has been tested, and it showed potent activity of histamine receptor antagonism.     

Examination of rofecoxib solution decomposition under alkaline and photolytic stress conditions

Rofecoxib is a highly active and selective cyclo-oxygenase II inhibitor. A stability-indicating method for the assay of rofecoxib has been developed using reverse-phase high-performance liquid chromatography (HPLC). Stress testing of rofecoxib was conducted during the method development and validation. HPLC analysis of rofecoxib solutions stressed under alkaline and photolytic conditions revealed the presence of several degradates. Two main degradates were determined to be the cyclization product formed by photo-cyclization and the dicarboxylate formed by ring opening in the presence of base and oxygen. The identities of these degradates were confirmed by comparison of UV spectra and HPLC retention time with the independently synthesized products. The mechanistic pathways for the formation of these degradates are discussed. Further improvement of the HPLC method's ruggedness has been made based on these studies.     

Effect of cocoa flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells

We previously showed that flavanols and their related oligomers (FLO) isolated from cocoa can have immunomodulatory effects on production of the cytokines interleukin-1beta (IL-1beta), IL-2, and IL-4. In the present study, we examined whether selected FLO fractions isolated from cocoa (monomer through decamer) modulate IL-5 protein secretion from resting and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Although FLO fractions were unstimulatory for IL-5 secretion in resting cells, PHA-induced IL-5 release from PBMC was markedly affected by certain FLO fractions. The monomeric and small oligomeric (dimer and trimer) fractions enhanced PHA stimulation by 50%, 54%, and 43%, respectively. In contrast, the larger oligomeric fractions (hexamer through decamer) inhibited IL-5 release in the range of 18% to 39%; the tetramer and pentamer showed intermediate effects. The increment in IL-5 suggests that FLO may preferentially stimulate immunoglobulin A. We suggest that in the oral cavity this could result in reduction in the risk for dental caries and periodontal disease. This work offers additional data for consideration of the health benefits of dietary FLO from a variety of foods, including those benefits associated specifically with consumption of some cocoas and chocolates.     

Dicaffeoyltartaric acid analogues inhibit human immunodeficiency virus type 1 (HIV-1) integrase and HIV-1 replication at nontoxic concentrations

The human immunodeficiency virus type 1 (HIV-1) is a major health problem worldwide. In this study, 17 analogues of L-chicoric acid, a potent inhibitor of HIV integrase, were studied. Of these analogues, five submicromolar inhibitors of integrase were discovered and 13 compounds with activity against integrase at less than 10 microM were identified. Six demonstrated greater than 10-fold selectivity for HIV replication over cellular toxicity. Ten analogues inhibited HIV replication at nontoxic concentrations. Alteration of the linkages between the two bis-catechol rings, including the use of amides, mixed amide esters, cholate, and alkyl bridges, was explored. Amides were as active as esters but were more toxic in tissue culture. Alkyl and cholate bridges were significantly less potent against HIV-1 integrase in vitro and were inactive against HIV-1 replication. Two amino acid derivates and one digalloylderivative of L-chicoric acid (L-CA) showed improved selectivity over L-CA against integration in cell culture. These data suggest that in addition to the bis-catechols and free carboxylic acid groups reported previously, polar linkages are important constituents for optimal activity against HIV-1 integrase and that new derivatives can be developed with increased specificity for integration over HIV entry in vivo.     

ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons

Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase family whose biological function in the CNS has not been defined. In contrast to ERK1 and ERK2, which are activated by neurotrophins (NTs), cAMP, and neuronal activity in cortical neurons, ERK5 is activated only by NTs. Here, we report that ERK5 expression is high in the brain during early embryonic development but declines as the brain matures to almost undetectable levels by postnatal day (P) 49. Interestingly, expression of a dominant-negative ERK5 blocked brain-derived neurotrophic factor protection against trophic withdrawal in primary cortical neurons cultured from embryonic day (E) 17 but not P0. Furthermore, expression of a dominant-negative ERK5 induced apoptosis in E17 but not P0 cortical neurons maintained in the presence of serum. We also present evidence that ERK5 protection of E17 cortical neurons may be mediated through myocyte enhancer factor 2-induced gene expression. These data suggest that ERK5 activation of myocyte enhancer factor 2-induced gene expression may play an important and novel role in the development of the CNS by mediating NT-promoted survival of embryonic neurons.     

Stability of magnesiowustite in Earth's lower mantle

Magnesiowüstite [(Mg,Fe)O] is the second most abundant mineral of Earth's lower mantle. Understanding its stability under lower mantle conditions is crucial for interpreting the physical and chemical properties of the whole Earth. Previous studies in an externally heated diamond anvil cell suggested that magnesiowüstites decompose into two components, Fe-rich and Mg-rich magnesiowüstites at 86 GPa and 1,000 K. Here we report an in situ study of two magnesiowüstites [(Mg(0.39),Fe(0.61))O and (Mg(0.25),Fe(0.75))O] at pressures and temperatures that overlap with mantle conditions, using a laser-heated diamond anvil cell combined with synchrotron x-ray diffraction. Our results show that addition of Mg in wüstite (FeO) can stabilize the rock-salt structure to much higher pressures and temperatures. In contrast to the previous studies, our results indicate that Mg-rich magnesiowüstite is stable in the rock-salt structure in the lower mantle. The physical and chemical properties of magnesiowüstite should change gradually and continuously in the lower mantle, suggesting that it does not make a significant contribution to seismic-wave heterogeneity of the lower mantle. Stable Mg-rich magnesiowüstite in lowermost mantle can destabilize FeO in the core-mantle boundary region and remove FeO from the outer core.     

Blood patch therapy for spontaneous intracranial hypotension: safe performance after epidurography in an unconscious patient

IMPLICATIONS: Epidurography was useful for identifying the epidural space and determining the likely spread of an epidural blood patch in an unconscious patient with spontaneous intracranial hypotension.