芳香稠环取代酰氯的合成

芳香稠环取代酰氯的合成胡文祥恽榴红张连锋（国防科工委军事医药研究发展中心，北京１００１０１；军事医学科学院毒物药物研究所，北京１００８５０）许多高效药物和激素用量甚少，分布全身代谢后血药浓度更低，并且它们又往往不含强烈的发色基团，因此在药代...     

Should endometrial polyps be removed in patients with postmenopausal bleeding?—an assessment of study designs and report of a failed randomised controlled trial (ISRCTN73825127)

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.     

The association of Triatoma maculata (Ericsson 1848) with the gecko Thecadactylus rapicauda (Houttuyn 1782) (Reptilia: Squamata: Gekkonidae): a strategy of domiciliation of the Chagas disease peridomestic vector in Venezuela?

Objective

To investigate the bioecological relationship between Chagas disease peridomestic vectors and reptiles as source of feeding.

Methods

In a three-story building, triatomines were captured by direct search and electric vacuum cleaner search in and outside the building. Then, age structure of the captured Triatoma maculata (T. maculata) were identified and recorded. Reptiles living in sympatric with the triatomines were also searched.

Results

T. maculata were found living sympatric with geckos (Thecadactylus rapicauda) and they bit residents of the apartment building in study. A total of 1 448 individuals of T. maculata were captured within three days, of which 74.2% (1 074 eggs) were eggs, 21.5% were nymphs at different stages, and 4.3% were adults.

Conclusions

The association of T. maculata and T. rapicauda is an effective strategy of colonizing dwellings located in the vicinity of the habitat where both species are present; and therefore, could have implications of high importance in the intradomiciliary transmission of Chagas disease.     

Tumorigenic potential of circulating prostate tumor cells

Circulating tumor cells (CTCs) have received intense scientific scrutiny because they travel in the bloodstream and are therefore well situated to mediate hematogenous metastasis. However, the potential of CTCs to actually form new tumors has not been tested. Popular methods of isolating CTCs are biased towards larger, more differentiated, non-viable cells, creating a barrier to testing their tumor forming potential. Without relying on cell size or the expression of differentiation markers, our objective was to isolate viable prostate CTCs from mice and humans and assay their ability to initiate new tumors. Therefore, blood was collected from transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and from human patients with metastatic castration-resistant prostate cancer (PCa). Gradient density centrifugation or red cell lysis was used to remove erythrocytes, and then leukocytes were depleted by magnetic separation using CD45 immunoaffinity beads. CTCs fractions from TRAMP mice and PCa patients were verified by immunocytochemical staining for cytokeratin 8 and EpCAM, and inoculated into immunodeficient mice. TRAMP tumor growth was monitored by palpation. Human tumor growth formation was monitored up to 8 months by ultrasensitive PSA assays performed on mouse serum. We found viable tumor cells present in the bloodstream that were successfully isolated from mice without relying on cell surface markers. Two out of nine immunodeficient mice inoculated with TRAMP CTCs developed massive liver metastases. CTCs were identified in blood from PCa patients but did not form tumors. In conclusion, viable CTCs can be isolated without relying on epithelial surface markers or size fractionation. TRAMP CTCs were tumorigenic, so CTCs isolated in this way contain viable tumor-initiating cells. Only two of nine hosts grew TRAMP tumors and none of the human CTCs formed tumors, which suggests that most CTCs have relatively low tumor-forming potential. Future studies should identify and target the highly tumorigenic cells.     

抗溃疡药瑞巴匹特的合成

目的：合成抗溃疡药２－（４－氯苯甲酰胺基）－３－（１,２－二氢－２－氧代－４－喹啉基）丙酸）瑞巴匹特）。方法：以乙酰乙酰苯胺为起始原料,经溴化,成环,取代,酸解,及缩合等五步反应合成该化合物。结果：合成产物经元素分析,经外光谱,核磁共振谱,质谱等确证。结论：此合成路线是完全可行的。     

Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal

Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4β2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.     

去氢表雄酮硫酸酯钠盐对妊娠大鼠子宫颈张力的影响及作用机理

去氢表雄酮硫酸酯为正常人体肾上腺所分泌,是合成雄激素和雌激素的前体。1970年日本钟仿制药厂正式生产该产品作为宫颈成熟剂,用于治疗宫颈成熟不全和产程延长等。Mochizuki给妊娠末期的妇女ⅳ去氢表雄酮硫酸酯钠盐(OHA-S)100 mg,共2次,发现DHA-S能促进子     

二苯乙烯类化合物对蛋白激酶C的抑制作用

报道15种二苯乙烯类化合物对蛋白激酶C(PKC)活性的影响。其中从中药金雀根中分得的3种二苯乙烯类低聚体α-viniferin,kobophenol A 和 miyabenolC,它们抑制PKC的IC₅₀分别为62.5,52.0和27.5μmol·L^-1。另外6种含酚羟基的二苯乙烯化合物对PKC也显示不同程度的抑制作用,但当酚羟基全甲基化或全乙酰化后其抑制作用大大降低甚至消失。酶动力学研究证明miyabenolC对PKC的抑制作用属于非竞争性抑制。     

超临界流体萃取法及高效液相色谱法分析延胡索中延胡索乙素的含量

采用超临界流体萃取法提取延胡索及其成方制剂中的延胡索乙素,以苯作改性剂,于40℃,42 MPa压力下,二氧化碳静态萃取5 min,动态萃取3 ml。该法操作简便快速,提取完全,也为其它中药及其制剂中有效成分的定量分析建立了一种简便、快速、有效的提取方法。应用硅胶柱─反相洗脱系统的高效液相色谱法测定延胡索及其成方制剂中延胡索乙素的含量,方法简便、快速、精密度高。此色谱系统同样适于其它中药及其制剂中生物碱的定量分析。     

Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline-DNA adducts by indole-3-carbinol: dose-response studies in the rat colon

Indole-3-carbinol (I3C) inhibits the formation of colonic aberrant crypt foci and DNA adducts in rats given heterocyclic amine colon carcinogens, such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Mechanism studies indicate that I3C induces cytochromes P4501A1 and 1A2 (CYP1A1 and CYP1A2), isozymes that respectively metabolize IQ via ring hydroxylation or activate the carcinogen by N-hydroxylation. The present study examined the dose-response for induction of CYP1A1 versus CYP1A2 by I3C, and compared the profiles of induction with the dose- response for inhibition of IQ-DNA adducts in the colon of the F344 rat. Dietary equivalent doses of I3C in the range 100-1000 p.p.m. increased in a dose-related manner both ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities in the liver and colonic mucosa, and Western blots showed a corresponding induction of CYP1A1 and CYP1A2 proteins. However, dietary equivalent doses of I3C in the range 10-25 p.p.m. (i) reduced hepatic EROD and MROD activities and CYP1A protein levels compared with controls, (ii) increased the ratio of CYP1A2 versus CYP1A1, and (iii) activated IQ to a more potent mutagen when liver microsomes from rats given I3C were used for metabolic activation in the Salmonella assay. Rats given a single oral dose of I3C shortly before administering IQ (5 mg/kg body wt, p.o.) exhibited dose-related inhibition of colonic IQ-DNA adducts in the range 25-100 p.p.m. I3C, reaching 95% inhibition at doses > or = 100 p.p.m. I3C, but IQ-DNA adducts were elevated slightly at the lowest I3C dose as compared with the controls. The possible significance of the low versus high dose effects of I3C are discussed in the context of human dietary exposures to I3C and the reported chemopreventive mechanisms of I3C in vivo.