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Byline: Hans-Christoph Diener (1), P. Tfelt-Hansen (2), C. Dahlof (3), M. J. A. Lainez (4), G. Sandrini (5), Sh.-J. Wang (6), W. Neto (7), U. Vijapurkar (7), A. Doyle (7), D. Jacobs (7) Keywords: placebo--controlled; migraine; topiramate; prophylaxis; propranolol Abstract: Abstract. Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo--controlled, dose--ranging trials. We conducted a randomised, doubleblind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double--blind treatment phase. Five hundred and seventy--five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles. Author Affiliation: (1) Department of Neurology, University Essen, Hufelandstr 55, 45122, Essen, Germany (2) Department of Neurology, University of Copenhagen Glostrup Hospital, Glostrup, Denmark (3) Gothenburg Migraine Clinic, Gothenburg, Sweden (4) Department of Neurology, Hospital Clinico Universitario University of Valencia, Valencia, Spain (5) Headache Centre IRCC C. Mondino Foundation, University of Pavia, Pavia, Italy (6) Neurological Institute Taipei, Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan (7) Johnson &amp Johnson, Pharmaceutical Research and Development, LLC Raritan, NJ USA Article History: Registration Date: 01/01/2004 Received Date: 02/01/2004 Accepted Date: 08/03/2004

Objective: The purpose of the current study was to investigate the roles of combined selenium and iodine deficiency in bone development as a possible experimental model of Kashin-Beck osteoarthropathy., Methods: Sprague-Dawley rats (n=48) were randomly divided into selenium deficiency (-Se+I), iodine deficiency (+Se-I), combined selenium and iodine deficiency (-Se-I), and selenium and iodine sufficient (+Se+I) groups. Growth of bone and cartilage, and the expression of type X collagen (ColX) and parathyroid hormone-related peptide (PTHrP) were measured in two generations of rats (F(0) and F(1))., Results: The tibial length in -Se-I rats was significantly shorter in F(1) generation. In +Se-I of F(1) rats, the thickness of the growth plate cartilage, and the proliferative zone was smaller, while in -Se-I rats the growth plate, and the proliferative and hypertrophic zones were also thinner in F(1) generation. In articular cartilage, ColX expression was increased in the deep zone in -Se-I rats of F(0) generation, and in -Se+I, +Se-I and -Se-I rats of F(1) generation. PTHrP expression was increased in the middle zone of -Se+I, +Se-I and -Se-I rats of both F(0) and F(1) generations. In the growth plate cartilage, ColX and PTHrP were expressed in the hypertrophic zone. ColX expression was significantly weaker in -Se+I and -Se-I rats in both F(0) and F(1) generations, while PTHrP expression was stronger in -Se+I, +Se-I and -Se-I rats in both F(0) and F(1) animals., Conclusions: Combined selenium and iodine deficiency impaired the growth of bone and cartilage. The changes in the expression of ColX and PTHrP induced by combined selenium and iodine deficiency were compatible to measurements of ColX and PTHrP in Kashin-Beck osteoarthropathy.