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991.
992.
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. 相似文献
993.
Mao B Abrahim A Ge Z Ellison DK Hartman R Prabhu SV Reamer RA Wyvratt J 《Journal of pharmaceutical and biomedical analysis》2002,28(6):1101-1113
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. 相似文献
994.
OBJECTIVE: To determine if group housing affects the variance of body composition parameters in a highly inbred mouse strain. RESEARCH METHODS AND PROCEDURES: Thirty 3-week-old male C57BL/6J mice were obtained from the Jackson Laboratory. Fifteen mice were housed individually, and 15 mice were housed in groups of 5/cage. Animals were fed ad libitum and maintained in the same room under a 12:12-hour light/dark photoperiod at 22 degrees C for 9 weeks. Animals were killed, and fat mass, soft-lean tissue mass, bone mineral density (BMD), and bone mineral content (BMC) were determined by DXA. At necropsy, weights of the paired epididymal fat pads, paired retroperitoneal fat pads, right inguinal fat pad, liver, kidneys, paired testes, and seminal vesicles were obtained. RESULTS: Relative to mice housed singly, group-housed mice showed significantly greater variance in percentage of body fat, testes weight, and BMC. Group-housed mice tended to show greater variance in liver weights and BMD. Mice housed singly were smaller, had less soft-lean tissue mass and BMC, and lower BMD when compared with group-housed mice. DISCUSSION: These results suggest that with respect to body composition parameters, mice housed singly are more similar to one another than are group-housed mice, most likely because of a reduction in environmental (predominately behavioral/social) effects. Thus, mice housed singly may be more representative of genotypic effects on body composition than group-housed mice. Whether other inbred strains of mice show similar responses to housing condition is unknown. 相似文献
995.
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. 相似文献
996.
997.
Reinke RA King PJ Victoria JG McDougall BR Ma G Mao Y Reinecke MG Robinson WE 《Journal of medicinal chemistry》2002,45(17):3669-3683
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. 相似文献
998.
There is controversy over potential effects of dopaminergic replacement therapies on the partially lesioned nigrostriatal dopaminergic projection. We evaluated indirect (levodopa, L-DOPA) versus direct (pramipexole, PRA) dopaminergic treatment effects on nigrostriatal lesion severity as measured with vesicular monoamine transporter type-2 (VMAT2) binding. Prior studies have shown that striatal VMAT2 density provides an objective estimate of dopaminergic neuronal integrity, without confounding effects of compensatory regulation. Partial unilateral median forebrain bundle lesions were made by injection of 6-hydroxydopamine in adult male Sprague-Dawley rats. Lesion severity was estimated using rotational behavior after injections of apomorphine and amphetamine. Rats were ranked and matched in pairs by rotation and assigned to receive either PRA (1 mg/kg/day) or L-DOPA/benserazide (100/25 mg/kg/day) ip via osmotic pump. After 4 weeks of drug treatment, in vitro autoradiography was performed with [(3)H]methoxytetrabenazine to measure striatal VMAT2 binding density. Lesion-to-intact VMAT2 density correlated with rotation in both treatment groups. There was no treatment effect on VMAT2 expression in the partially lesioned striatum and thus no differential effect of indirect versus direct dopamimetic treatment on nigrostriatal integrity. 相似文献
999.
1000.
ERK5 activation of MEF2-mediated gene expression plays a critical role in BDNF-promoted survival of developing but not mature cortical neurons 总被引:10,自引:0,他引:10
Liu L Cavanaugh JE Wang Y Sakagami H Mao Z Xia Z 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(14):8532-8537
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. 相似文献