高选择性环氧化酶—2抑制剂的进展与评价

目的 :介绍高选择性环氧化酶 - 2抑制剂———昔布类药物进展 ,并评价其临床疗效 ,以供临床参考。方法 :查阅国内、外近期相关文献进行分析、评价。结果与结论 :昔布类高选择性环氧化酶 - 2抑制剂进展十分迅速 ,对环氧化酶 - 2的选择性高 ,在治疗骨关节炎和类风湿性关节炎、关节痛、术后疼痛和肿瘤上展现了良好的治疗前景     

中药“三宝素”对小白鼠细胞免疫功能的增强作用

三宝素经动物实验证明,具有显著增强小鼠细胞免疫功能的作用。本品还有抗疲劳、安神及镇静作用;而无毒、无致畸、无致癌等副作用     

Clearance of diazepam can be impaired by its major metabolite desmethyldiazepam

Summary The pharmacokinetics of a single intravenous dose of diazepam 0.1 mg/kg was studied in 6 healthy volunteers, in random order under controlled conditions and following pretreatment with its major metabolite, desmethyldiazepam (20 mg/day) for one week. In the two subjects with the highest plasma concentration of desmethyldiazepam (990 and 1100 ng/ml, respectively), total plasma clearance (Cl) of diazepam was reduced after desmethyldiazepam, by 31% and 54%, respectively. In three individuals there was a moderate decrease of 14% to 21%, and no effect was seen in one volunteer. Cl was significantly reduced (11.5±1.8 vs. 9.1±3.3 ml/min;p=0.015) and elimination half-life tended to be prolonged (38.5±10.4 vs. 65.8±67.1 h;p=0.15). It is concluded that high concentrations of desmethyldiazepam can influence the elimination of its parent drug diazepam by product inhibition.     

Effect of Non-Thermal Plasma Treatment of Contaminated Zirconia Surface on Porphyromonas gingivalis Adhesion and Osteoblast Viability

Plasma treatment on a zirconia surface prevents bacterial contamination and maintains osteoblast activity. To assess the degree of adhesion of Porphyromonas gingivalis on a zirconia surface after non-thermal plasma (NTP) treatment, specimens were treated with plasma for 60, 300, and 600 s, after which P. gingivalis was inoculated onto the surface and incubated for 48 h. To assess osteoblast activity after NTP treatment, osteoblasts (MC3T3-E1) were dispensed onto the specimens contaminated with P. gingivalis immediately after NTP for 60 and 120 s, followed by incubation for 48, 72, and 96 h. P. gingivalis was cultured after 60 s of NTP treatment of zirconia. The NTP and control groups showed no significant difference (p = 0.91), but adhesion was significantly increased following NTP treatment for 300 s or longer (300, 600 s groups) (p < 0.05). After NTP treatment of P. gingivalis-contaminated zirconia, osteoblast activity significantly increased at 72 and 96 h (I60 and I120 s group) in the groups treated with plasma (p < 0.017). Application of NTP to dental zirconia implants for 60 s not only inhibits the proliferation of P. gingivalis, which causes peri-implantitis but also increases osseointegration on zirconia surfaces contaminated with P. gingivalis.     

The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

香菇和黄芪混合多糖抑制S—180肉瘤生长和增强免疫作用的研究

经口给予香菇多糖与黄芪多糖混合物，抑制动物移植性肿瘤重复实验结果一致显示，香菇多糖与黄芪多糖混合物在１５０．０ｍｇ／ｋｇ．ＢＷ／ｄ剂量时可以抑制Ｓ—１８０移植性肉瘤的生长；小鼠腹腔巨噬细胞吞噬鸡红细胞作用实验显示，香菇多糖与黄芪多糖混合物在３７．５ｍｇ／ｋｇ．ＢＷ／ｄ剂量（及以上剂量）时具有提高小鼠吞噬细胞功能的作用；小鼠脾ＮＫ细胞活性测定结果表明，香菇多糖与黄芪多糖混合物在３７．５ｍｇ／ｋｇ．ＢＷ／ｄ剂量（及以上剂量）时具有增强ＮＫ细胞活性的作用。且上述三个实验均显示良好的剂量—反应关系     

Application of Saliva Inhibition to Detect Underlying Alloantibodies in Bombay Blood Group

IntroductionThe Bombay phenotype is a rare blood group determined by the absence of H antigens. Bombay individuals produce anti-H, a clinically significant antibody that react against all ABO blood group. Anti-H can mask underlying alloantibody during antibody investigation, a challenge in current transfusion practice. The aim of this article is to explore saliva inhibition, a novel method to detect underlying alloantibody in Bombay individuals.Case PresentationThe case is a 93-year-old female transfused with pre-donated autologous blood for a surgery. We determined anti-H subclass and thermal amplitude, secretor status, and optimal ratio of saliva and Bombay plasma. Plasma samples containing anti-H were spiked with anti-Fy(a) to determine the effectiveness of saliva inhibition in uncovering underlying alloantibodies.ResultsAnti-H was confirmed to be predominately IgM with broad thermal amplitude. Tube immediate spin (IS) showed stronger anti-H reactivity compared to column agglutination technology (CAT). Spiked anti-Fy(a) was successfully detected using saliva inhibition method.ConclusionTube IS appears more sensitive to anti-H. Saliva inhibition appears to be a promising method to detect underlying alloantibody in the plasma of Bombay phenotype individuals.     

Benzimidazole-2-Phenyl-Carboxamides as Dual-Target Inhibitors of BVDV Entry and Replication

Bovine viral diarrhea virus (BVDV), also known as Pestivirus A, causes severe infection mostly in cattle, but also in pigs, sheep and goats, causing huge economical losses on agricultural farms every year. The infections are actually controlled by isolation of persistently infected animals and vaccination, but no antivirals are currently available to control the spread of BVDV on farms. BVDV binds the host cell using envelope protein E2, which has only recently been targeted in the research of a potent and efficient antiviral. In contrast, RdRp has been successfully inhibited by several classes of compounds in the last few decades. As a part of an enduring antiviral research agenda, we designed a new series of derivatives that emerged from an isosteric substitution of the main scaffold in previously reported anti-BVDV compounds. Here, the new compounds were characterized and tested, where several turned out to be potent and selectively active against BVDV. The mechanism of action was thoroughly studied using a time-of-drug-addition assay and the results were validated using docking simulations.     

大学新生抑郁与行为抑制/激活系统及心理弹性的关系

目的 探讨大学新生抑郁与行为抑制/激活系统、心理弹性的关系,为抑郁干预提供参考依据.方法 采用分层随机抽样,利用贝克抑郁自评量表(Beck depression inventory-Ⅱ,BDI-Ⅱ)、行为抑制/行为激活系统(behavioral inhibition system/behavioral activation system,BIS/BAS)量表中文版、心理弹性量表中文版对某高校570名大一新生进行调查.结果 新生抑郁与BIS成正相关(r=0.22,P＜0.01);与心理弹性3个因素成负相关(r=-0.43～-0.35,P＜0.01).不同程度抑郁症状组的BIS及心理弹性3个因素相比,差异有统计学意义(P＜0.01).力量、BIS、乐观性可有效预测新生抑郁,总解释率为22％.结论 大学新生抑郁与BIS/BAS、心理弹性密切相关,高BIS和低心理弹性可有效预测抑郁.     

神经节苷脂GM_1和GM_3对受体介导的转铁蛋白内吞过程的影响

我们从正常人脑及肝脏中分离得到纯化的神经节苷脂GM_1[Gal-GalNAc-(NeuNAc)Gal-Glc-Cer]和GM_3[NeuNAc-Gal-Glc-Cer],发现外源性GM_1或GM_3的加入能不同程度地抑制SMMC-7721人肝癌细胞的生长,但仅GM_3能抑制转铁蛋白(Tf)促进的细胞生长。进一步的研究发现,GM_3并不影响Tf与细胞膜表面受体的结合,而是抑制了受体介导的Tf内吞过程,内吞囊泡的形成及融合均受到影响。结果提示:GM_3在膜中的嵌入,可能使受体的构象发生变化或影响了膜的流动性,从而抑制Tf的内吞过程。