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41.
D Komiotis C T Lim J P Dieter G C Le Breton D L Venton 《Journal of medicinal chemistry》1992,35(16):3033-3039
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. 相似文献
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44.
Brigitte Schiller Chun He David J. Salant Alice Lim Jessy J. Alexander Richard J. Quigg 《The Journal of experimental medicine》1998,188(7):1353-1358
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. 相似文献
45.
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. 相似文献
46.
47.
Sergio J Canovas Eric Lim Fernando Hornero Jose Montero 《European journal of cardio-thoracic surgery》2003,23(4):639-641
Left ventricular free wall rupture is a dramatic complication after myocardial infarction. We present our experience with the simple, expedient technique of patch glue repair without extracorporeal circulation. Access is obtained via median sternotomy. Evacuation of blood and haematoma is undertaken and a Goretex patch exceeding the size of infarct is fashioned. The patch is applied to the epicardium using enbrucrilate surgical glue instilled with gentle pressure against the beating heart. We performed this technique on 17 patients from 1993 to 2001, with a operative (30-day) mortality of 23.5% with a post-discharge survival of 85% at 2.2 years. 相似文献
48.
A double-blinded study was conducted to compare the effects of mupirocin and tetracycline ointments in the treatment of skin infections. 111 patients were available for clinical assessment, of which 53 were treated with mupirocin and 58 treated with tetracycline. Clinically, both groups were improved, and there was no significant difference. Bacteriological assessment however revealed a better response to mupirocin. Staphylococcus aureus and Streptococcus pyogenes were the most common organisms isolated. 99% of Staphylococci were sensitive to mupirocin compared with 61% to tetracycline and 29% to penicillin G. 57% of Group A beta haemolytic Streptococci were resistant to tetracycline compared to 14% to mupirocin. Gram-negative organisms were mostly resistant to both preparations. No side effects were observed in both treatment groups. This study suggests that mupirocin is a safe and effective topical preparation for treating most of our common skin infections. 相似文献
49.
Claudia KY Lai 《BMC nursing》2007,6(1):5
Background
To date, the literature has provided an abundance of evidence on the adverse outcomes of restraint use on patients. Reportedly, nurses are often the personnel who initiate restraint use and attribute its use to ensuring the safety of the restrained and the others. A clinical trial using staff education and administrative input as the key components of a restraint reduction program was conducted in a rehabilitation setting to examine whether there were any significant differences in the prevalence of restraint use pre- and post-intervention. Subsequent to the implementation of the intervention program, focus group interviews were conducted to determine the perspective of the nursing staff on the use of restraints and their opinions of appropriate means to reduce their use. 相似文献50.
Initial management of acute urethral injuries 总被引:1,自引:0,他引:1
A study was made of 30 cases of acute urethral trauma treated over a 7-year period. There were 10 anterior and 20 posterior urethral injuries, the majority of these being partial ruptures. Posterior urethral injuries were caused by road traffic accidents in 75% of cases while 80% of the anterior urethral injuries were of the "straddle" type. There was only 1 case of iatrogenic injury to the anterior urethra. During follow-up, all patients required periodic dilatations for stricture except for the single case of iatrogenic injury. An average of 5 dilatations controlled all of the strictures except for 2 that required urethroplasties. 相似文献