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R.M. Sawaya and D.S. Riddick Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8. rana.sawaya utoronto Aromatic hydrocarbons AHs ; , such as 3-methylcholanthrene MC ; , elicit toxic and adaptive responses via the aryl hydrocarbon receptor AHR ; . AHs suppress the transcription of the growth hormone-regulated, male-specific rat hepatic cytochrome P450 2C11 gene CYP2C11 ; via an unknown mechanism. Structure-activity analysis suggests the involvement of the AHR in CYP2C11 suppression. We hypothesize that the in vivo suppression of CYP2C11 by AHs is mediated by the gene's promoter and 5'flanking region. Following bioinformatic analysis of putative transcription factor TF ; binding sites, we cloned various lengths up to 10kb ; of the CYP2C11 5'-flank into a promoterless luciferase plasmid. Using high-volume tail vein injections to deliver plasmid to the liver of live rats, we studied the AH-responsiveness of luciferase constructs containing 10.1-kb and 2.4-kb of the CYP2C11 5'-flank. MC treatment suppressed CYP2C11-driven luciferase activity of the 10.1-kb construct to 48% of control levels by 24h and to 31% by 72h after treatment. The luciferase activity of the construct containing 2.4-kb of the CYP2C11 5'-flank was not suppressed by MC indicating that negative regulatory element s ; responsible for CYP2C11 reporter suppression by MC exist between -10.1 and -2.4-kb. Trends for corresponding decreases of endogenous CYP2C11 protein and mRNA were detected by immunoblotting and real-time PCR; however, this did not always reach statistical significance. As a positive control for AHR activation, MC dramatically induced the luciferase activity of a Cyp1a1-driven luciferase plasmid under AHR control. This is the first demonstration of the suppression of a CYP2C11 luciferase construct by an AH and this finding suggests that the 5'-flanking region and promoter mediates the down-regulation of this gene in the intact rat. [Support: CIHR] and elavil.
The reimbursement level, which is on average 65% of price paid by the customer, is due to change by mid-2003. The major change is that the generic price level always 30% less than the brand name product ; will become the reference price for the 65% reimbursement level. This change will allow generics to increase their market share from 4% to 15-20% of the French non-hospital pharmaceutical market. Enhanced generic substitution is also being demanded of doctors as a pay-off for the recent increase in consultation fees. The de-listing of 800 reimbursed drugs mainly vein tonics ; on risk-benefit grounds is expected in the coming three years. On the positive side, incentives are promised for new innovative products.
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The authors thank Cleopatra Alvaro, Ryan Descallar, Leo Angelo Ocampo, Gloria Oracoy and Florence Tolentino for their invaluable contribution to data collection and data processing, and Josephine Parinas for administrative assistance. Also, the authors thank the Department of Health of the Philippines for endorsing the project, and the directors and staff of the Central and Regional Hospital Licensing Units of the Department of Health for their assistance with data access. This research is supported by The David and Lucile Packard Foundation. The findings and conclusions expressed are entirely those of the authors, and do not necessarily represent the views of The David and Lucile Packard Foundation and caduet.
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To achieve the overall goal of eliminating unsafe abortion, the participants at the consultation identified priority topics and activities in research, capacitybuilding, norms and tools, and advocacy to reduce the burden of unsafe abortion on women, their families, and health systems. The participants made recommendations in four main areas: 1 ; biomedical research and the introduction of medical abortion technologies, 2 ; social, behavioural, and health systems research, 3 ; programmes and policies, and 4 ; advocacy. The participants acknowledged that defining priorities is often a challenge, given that the problems associated with unsafe abortion are subject to shifts in social and legal contexts over a period of time and that, to a greater extent than with many other reproductive health issues, unsafe abortion is a regional matter. This call for action reflects recent thinking on issues associated with unsafe abortion, including topics that are relevant globally or in some cases, for specific regions only and ascorbic.
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1.World Health Organization and Health Action International. Medicine prices: a new approach to measurement. Working draft for field testing and revision. 2003 edition. 2. SL Hu. Pharmaceutical Cost-containment Policy: Experiences in Shanghai, China. Health Policy and Planning; 2001, 16 Suppl 2 ; : 4-9. 3. Qinyue Meng. The impact of china's retail drug price control policy on hospital expenditures. Oxford university press in association with the London School of Hygiene and Tropical Medicine. 2005: 185-196. 4. The State Development and Reform Committee. Drug pricing policy collection. Apr. 2006. 5. Sun Qiang. A Survey of Medicine Prices, Availability, Affordability and Price Components in Shandong Province, China. Oct. 2005 and chlorthalidone.
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