ABSTRACT
BACKGROUND: Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as 'ciliotherapy'. METHODS AND RESULTS: In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopaminergic agonist to regulate cilia length and function. Our in vivo studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients. CONCLUSIONS: Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia.
ABSTRACT
OBJECTIVE: This project was designed to evaluate the effects of melatonin and zinc on the glycemic control in type 2 diabetes mellitus (T2DM) patients with inadequate response to the oral hypoglycemic agent metformin. METHODS: A placebo controlled, double-blind clinical trial was performed at the Specialized Center for Endocrinology and Diabetes, Al-Rusafa Directorate of Health, Baghdad, Iraq during the period from February to July 2005, in which 46 type 2 diabetic patients were selected and allocated into 3 groups, these groups were treated with single daily oral doses of both 10 mg melatonin and 50 mg zinc acetate alone; 10 mg melatonin and 50 mg zinc acetate in addition to the regularly used metformin or placebo, given at bed time for 90 days. We measured the fasting plasma glucose (FPG), glycated hemoglobin (HbA1C) and serum C-peptide before starting the treatment (zero time) and after 30 and 90 days of treatment. We also performed post-prandial glucose excursion test (PPGE) for selected patients from the second and third groups before starting the treatment and after 90 days. RESULTS: Daily administration of melatonin and zinc improved the impaired fasting and post-prandial glycemic control and decreased the level of glycated hemoglobin; addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. CONCLUSION: The combination of melatonin and zinc acetate, when used alone or in combination with metformin improves fasting and post-prandial glycemic control in T2DM patients.
