PgH2 analogs as potential antiplatelet derivatives.

Previous observations implicating PgH2 as a direct activator of platelets suggested that derivatives of U46619, a well-characterized TxA2 receptor agonist having structural homology with PgH2, might possess antiplatelet activity. The present work describes the synthesis of [1S-(1 alpha,2 beta,3 alpha,4 alpha)]-3-[(tetrahydropyranyloxy)methyl]- 2-[2-[(triphenylmethyl)oxy]ethyl]-5-oxabicyclo[2.2.1]heptane (14) a potentially useful intermediate for the synthesis of various epoxymethano derivatives. The latter was converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7-[3-[[2- [(phenylamino)carbonyl]-hydrazino]methyl]-5-oxabicylo[2.2.1]hept-2 - yl]-5-heptenoic acid (23), an epoxymethano derivative of PgH2 containing a hydrazide lower side chain as previously used in the TxA2 antagonist, SQ 29,548. The intermediate 14 was also converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7- [3-[(hexylamino)methyl]-5-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (25) which contained a simple aza side chain as used in earlier antagonists. Derivatives 23 and 25 appeared to be specific antagonists of the human platelet TxA2 receptor as evidenced by their inhibition of U46619 (1.5 microM) induced aggregation of human platelet rich plasma (IC50 = 22 and 7 microM, respectively), while having little effect on ADP (2 microM) induced aggregation at much higher concentrations. In addition, one of these derivatives, the bicycloamine 25, was shown to compete for [3H]U46619 binding to washed human platelets with an IC50 value of 25 microM, supporting the notion that these derivatives were acting at the thromboxane receptor. However, the potency of these derivatives was less than for previously reported TxA2 antagonists, suggesting that simple linear combinations of functionality from molecules active at the human platelet thromboxane receptor will be of limited predictive value.     

云南省卫生资源配置标准的弹性系数研究

目的　在进行云南省区域分类基础上制定云南省区域卫生资源配置标准标志值后 ,根据云南省各个地区的特点增加不同弹性系数。方法　采用流行病学研究方法 ,收集和分析云南省不同地州市 1990～ 1999年有关人口、社会经济状况及卫生经费的投入、居民健康状况、居民文化、生活水平、少数民族状况、旅游地区、边境线长短及贫困状况等资料。结果　研究结果表明曲靖地区、玉溪市、保山地区增加弹性系数最少 ,分别为 0 67%、 1 5 8%和1 68% ,怒江州、迪庆州和西双版纳州增加弹性系数最多 ,分别为 11 15 %、 10 2 5 %和 9 84 %。其它地区的弹性系数分别为昆明市 5 88% ,昭通地区 2 3 1% ,楚雄州 2 3 0 % ,红河州 7 0 3 % ,文山州 5 5 3 % ,思茅地区 7 4 3 % ,大理州4 94 % ,德宏州 6 78% ,丽江地区 4 3 5 % ,临沧地区 6 13 %。结论　云南省区域卫生配置标准的弹性系数研究为云南省卫生资源区域分类配置标准提供了科学依据 ,不同弹性系数体现了云南省不同地区的卫生资源区域分类配置标准的公平性、合理性及实用性     

Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis

Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface.     

Tamoxifen suppresses tumor promoter-induced hydrogen peroxide formation by human neutrophils.

Trans-tamoxifen (TAM) has been used successfully in therapy for estrogen-dependent human breast tumors and prevention of their recurrence. The mechanism of this prevention was thought to be due to the interference of TAM with estrogen promotion. TAM has a wider anticarcinogenic action that is similar to other chemopreventive agents in that it suppresses tumor promotion in 2-stage carcinogenesis by interfering with the action of protein kinase C. We report that TAM (5 microM) totally inhibits hydrogen peroxide (H2O2) formation by 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-treated human neutrophils. Interestingly, beta-estradiol (10 microM) also slightly inhibits the oxidative burst of neutrophils. Pretreatment of neutrophils with varying amounts of TAM and beta-estradiol caused additive inhibition of H2O2 formation by the 2 agents. 4-Hydroxy-tamoxifen, a metabolite with the highest affinity for the estrogen receptor, was only as inhibitory as beta-estradiol. Other derivatives (cis-, N-desmethyl-, and N-desdimethyl-tamoxifen) with low biological activities had a smaller effect on H2O2 formation. TPA-treated neutrophils were shown to contain 5-hydroxymethyl uracil (HMU). TAM prevented the TPA-induced formation of HMU in other cells. Like TPA, dietary fat, which is a risk factor for breast cancer, induces formation of HMU in the DNA of human white blood cells. TAM may suppress the dietary fat-induced HMU in the same manner at it does in TPA-induced neutrophils.     

33例精神分裂症患者氯丙嗪治疗前后血小板聚集功能

本文对精神分裂症患者用氯丙嗪治疗前后PAg(T)功能进行观察及BPRS评定,发现精分症患者PAg(T)功能明显高于对照组,用氯丙嗪治疗1个月后,BPRS评定分值下降,患者临床症状消除,而PAg(T)第一时相无变化,第二时相明显升高,说明氯丙嗪聚药物可促发血小板释放内源性致聚物质,同时也说明患者PAg(T)异常不仅仅是情绪应激所致,更重要的是血小板生理功能异常。     

Recurrent lens binding and central island formations in a fast-responding orthokeratology lens wearer.

A 12-year-old girl with a history of fast myopia progression underwent advanced orthokeratology (ortho-k) treatment and suffered from recurrent lens binding and central corneal staining. The problem could not be fixed by lens fenestration and refitting with a less aggressive lens (three-zone ortho-k) design. After refitting with a lower target advanced ortho-k lens, these complications were no longer occurring, and the amount of power reduction was greater than expected considering the target designed for the refitted lenses. During the following 15 months of ortho-k lens wear, there was no clinically significant change to her refractive error. The patient and her parents were happy with the outcome, although the refractive error was not totally eliminated and she still needed to wear spectacles for clear vision. Possible etiologies of the complications are discussed.