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991.
992.
Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function 总被引:2,自引:0,他引:2
Cid MC Esparza J Schnaper HW Juan M Yague J Grant DS Urbano-Márquez A Hoffman GS Kleinman HK 《Angiogenesis》1999,3(3):271-280
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood
vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data
suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17β-estradiol
increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen,
type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic
peptides containing an RGD sequence. Upon exposure to estradiol, an increase in β1, α5 and α6 integrin mRNA was observed in
subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement
in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since
an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated
endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation,
the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens
can promote neovascularization and vessel repair.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
993.
BACKGROUND AND OBJECTIVES: Crack-smoking sexually transmitted disease (STD) patients are at high-risk for contracting HIV. GOAL OF THE STUDY: To examine the effects of cocaine use and other correlates on high-risk sexual behavior among STD clinic patients. STUDY DESIGN: This was a cross-sectional study of 1,490 consecutive patients attending three Los Angeles County STD clinics between 1992 and 1994. RESULTS: Logistic regression analysis found high-risk sexual activity was associated with being a male and being of younger age. Among women, high-risk sexual behavior was associated with crack cocaine use and a perceived need for help. Among the men in the study, ethnicity (being black) and having an arrest history were associated with high-risk behavior. CONCLUSIONS: Effective intervention strategies should address cocaine use among STD patients and provide them with referrals to drug treatment. 相似文献
994.
995.
Because of various pharmacodynamic properties, such as the nonlinearity of the concentration-effect relationship, activation of feedback homeostatic mechanisms, induction of pharmacodynamic tolerance, etc., administration of the same dose of drug by different modes is expected to produce different outcomes. This review clarifies the theoretical and practical aspects of the impact of different modes of drug administration on the magnitude of response, and hence on therapy outcomes. It discusses how the interrelationship between the pharmacodynamic properties and the drug input function affects the magnitude of response. To demonstrate this special dimension of drug therapy, relevant pharmacodynamic data was obtained for drugs with different therapeutic applications, including antibiotics, analgesics, diuretics, anti-cancer, anti-ulcer, anti-inflammatory, anti-hypertensive, lipid-lowering anti-parkinsonian, and immunosuppressive drugs. These examples provide guidelines for implementing the role of the mode of drug administration (including rate, schedule, and route of drug treatment) during drug development or optimization of drug therapy. 相似文献
996.
Due to its availability as an over-the-counter drug, the use of cimetidine is increasing, thus adverse interactions with other commonly used agents may also increase. The aim of this study was to investigate whether acute administration of cimetidine could alter the pharmacodynamics of theophylline neurotoxicity and the hypnotic action of ethanol.To examine these questions, rats received a dose of 77 mg/kg cimetidine followed by a constant infusion of either theophylline (1.2 mg/min.) or ethanol (16.3 mg/min.) until the onset of the pharmacological end point, maximal seizure or loss of righting reflex, where samples of blood and brain were obtained and assayed for either theophylline or ethanol. We report that cimetidine in doses that may cause pharmacokinetic interactions did not affect the concentration-effect relationship of either the stimulating action of theophylline or the depressant activity of ethanol. These outcomes emphasize the relative safety which patients using cimetidine in self-medication rely on. 相似文献
997.
Seymour RA Watkinson H Hawkesford JE Moore U 《European journal of clinical pharmacology》2000,55(11-12):801-806
OBJECTIVE: To evaluate in a randomised, double-blind, placebo-controlled trial, the efficacy (time to onset of meaningful pain relief) of single doses of buffered ketoprofen (12.5 mg) and ibuprofen (200 mg) in 180 patients with postoperative pain after third molar surgery. METHODS: 180 adult patients who had undergone third molar surgery under general anaesthesia participated in this study. After dosing, patients recorded their time to meaningful pain relief, pain intensity on both visual analogue scales and verbal rating scales, pain relief and the need for additional analgesia. Pain recordings were made at fixed time points over a 6-h investigation period. RESULT: Buffered ketoprofen (12.5 mg) provided quicker meaningful pain relief than placebo (P = 0.023). For secondary efficacy measures (SPIDS4, SPIDS6, TOTPAR4, TOTPAR6), the buffered ketoprofen was significantly superior to both placebo (P < 0.001) and ibuprofen (200 mg) (P < 0.05). Similarly, the amount of time before taking an escape analgesic was significantly less in the placebo group than both the ibuprofen and buffered ketoprofen groups (P < 0.03). CONCLUSIONS: Buffered ketoprofen (12.5 mg) provides effective pain control in the early postoperative period after third molar surgery. This ketoprofen preparation was also superior to ibuprofen (200 mg) with respect to both reducing pain intensity and providing an earlier onset of pain relief. 相似文献
998.
This study was conducted to assess whether the parallel Michaelis-Menten and first-order elimination (MM+FO) model fitted the data better than the Michaelis-Menten (MM) model, and to validate the MM+FO model and its parameter estimates. The models were fitted to 853 steady state dose: serum concentration pairs obtained in 332 adults with epilepsy using nonlinear mixed-effects modeling (NONMEM). The MM+FO model fitted the data better than the MM model. The validity of the pharmacokinetic models and the estimated population parameter values was tested using the naive prediction method. The estimation and validation of the pharmacokinetic parameters were undertaken in two separate patient groups (cross-validation) obtained by splitting the data set. Patients were randomly allocated to two equally matched groups (groups 1 and 2). The predictive performance was assessed using 770 paired predicted versus actual dose or measured serum concentrations. The population pharmacokinetic parameters estimated by NONMEM in group 1 were validated in group 2 and vice versa. When predicting steady state serum concentration, the MM+FO model was clearly superior to the MM model (mean bias of 0.91 and 8.13 mg/L, respectively). 相似文献
999.
Amrani Y Lazaar AL Hoffman R Amin K Ousmer S Panettieri RA 《Molecular pharmacology》2000,58(1):237-245
1000.
Zhang X Hodgetts K Rachwal S Zhao H Wasley JW Craven K Brodbeck R Kieltyka A Hoffman D Bacolod MD Girard B Tran J Thurkauf A 《Journal of medicinal chemistry》2000,43(21):3923-3932
The dopaminergic receptor profile of a series of trans-1-[(2-phenylcyclopropyl)methyl]-4-arylpiperazines was examined. Aromatic substitution patterns were varied with the goal of identifying a compound having affinities for the D(2) and D(4) receptors in a ratio similar to that observed for the atypical neuroleptic clozapine. The compounds (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dichlorophenyl)piperazine (5m) and (1S, 2S)-trans-1-[(2-phenylcyclopropyl)methyl]-4-(2, 4-dimethylphenyl)piperazine (5t) were selected for functional antagonists at D(2) and D(4) receptors and had a D(2)/D(4) ratio approximating that of clozapine; they proved inactive in behavioral tests of antipsychotic activity. 相似文献