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A 03 PROGRESSION FROM MILD FIBROSIS TO CIRRHOSIS IS ASSOCIATED WITH INCREASED BCL-2 AND PIAS3 AND DECREASED STAT3 AND CYCLIND1 EXPRESSION IN HEPATITIS C INFECTED LIVERS. P. Starkel, C. De Saeger, I. Leclercq, Y. Horsmans. Department of Gastroenterology, St. Luc University Hospital, Brussels, Belgium. Background : In vitro and animal data suggest that HCV proteins might interfere with Stat3 signalling. However, only limited data are available concerning Stat3 expression and its association with cellular proliferation and apoptosis in human liver. Aim : We examined expression of Stat3 and proteins involved in controlling Stat3 signalling as well as cell cycle and apoptosis markers in human livers infected with HCV at various stages of fibrosis progression. Methods : Human liver biopsies matched for inflammatory scores without fibrosis or with mild fibrosis or established cirrhosis were examined for expression of Stat3, Socs3, Pias3, cyclin D1, Bcl-2, and Bax. Protein expression in liver homogenates was determined by Western blotting and Mrna levels by quantitative PCR. Results : Stat3 protein expression started to decreased with appearance of fibrosis and was significantly lower in established cirrhosis compared to liver biopsies without fibrosis. In addition, Pias3 protein and Mrna expression increased progressively with the progression from mild fibrosis to cirrhosis whereas Socs3 Mrna dropped only significantly once cirrhosis has been established. In parallel, cyclin D1 protein expression decreased and Bcl-2 increased progressively with appearance of fibrosis both being significantly different in established cirrhosis compared to biopsies without fibrosis. Cyclin D1 correlated significantly with Stat3 expression R2 0.61 ; p 0.001 ; whereas no correlation was found between Bcl-2 and Stat3. Bax expression did not change significantly. Conclusion : Disturbances in Stat3 signalling might contribute to progression from mild fibrosis to cirrhosis in HCV infected livers possibly through disturbed cell cycle progression that is only insufficiently compensated by activation of anti-apoptotic pathways. Take history and examine for genital ulcers and whether prepuce is retractable and estrace!

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Educator's Copy 1. Dear Expert: Pat and I have been dating for four months. Pat is really wonderful and really wants to have sex with me, but I'm just not sure. How do I know if I'm ready? feelings for Pat personal values e.g. cultural, religious ; alternatives to intercourse looking back: will you feel good about decision? prepared to take responsibility with birth control and STI prevention? 2. Dear Expert: I just had sex for the first time last weekend. Sam is really wonderful, but I kind of regret having sex. I don't know if I want to continue a sexual relationship. But now that I've "done it, " I guess there is no going back. What should I do? just because you said yes once does not mean you have to say yes again freedom to say yes or no important to communicate concerns to Sam alternatives to intercourse 3. Dear Expert: My boyfriend and I started going out a few months ago. Our relationship is great, but he always wants to hold my hand and kiss me when we're in public, and I don't feel comfortable with that. What should I do? important to do what's right for you important to talk to each other 4. Dear Expert: I've been going out with Sue for ten months. She always threatens to break up with me if I don't have sex with her. Sometimes I don't feel like it. I tried to talk to her about it, but she just won't listen. I'm worried she'll spread nasty rumours about me. What should I do? abuse issues freedom to say yes or no important to get support from trusted friend adult may need to end relationship.

The management of diabetes hinges on the commitment of the person with diabetes to selfmanagement, balancing appropriate lifestyle choices, self-monitoring of blood glucose levels, and pharmacologic or insulin therapy. To support patient self-management, the physician should: Encourage the patient to accept responsibility for the care of their diabetes Reinforce the importance of lifestyle modifications including healthy eating, active living exercise, weight management, social support and smoking cessation Encourage the use of diaries or logbooks Help the patient identify a support team Refer the patient to the local Diabetes Education Centre Define, with the patient, the best possible goals such as blood glucose concentration, A1C, blood pressure, lipids, lifestyle modifications and appropriate follow-up Provide the patient with appropriate, individualized education culturally sensitive information, skills and support. I don't think there's going to be a huge move to this drug, added dr.

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