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Kathem S.H.,University of Toledo | Kathem S.H.,University of Baghdad | Mohieldin A.M.,University of Toledo | Abdul-Majeed S.,University of Toledo | And 8 more authors.
Journal of Geriatric Cardiology | Year: 2014

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. ©2014 JGC All rights reserved. Source


Kobayashi S.,Kidney Disease and Transplant Center | Mochida Y.,Kidney Disease and Transplant Center | Ishioka K.,Kidney Disease and Transplant Center | Oka M.,Kidney Disease and Transplant Center | And 4 more authors.
Hypertension Research | Year: 2014

Cognitive dysfunction is prevalent in chronic kidney disease patients. Little is known about the relationship between the regional cerebral blood flow (rCBF) and cognitive function in hemodialysis (HD) patients. We used quantitative single-photon emission-computed tomography (SPECT) to determine whether rCBF decreased in these patients. Fifty-four consecutive HD patients who were able to visit the hospital unassisted and had no history of stroke underwent cognitive assessment based on the Mini Mental State Examination (MMSE). Using quantitative image-analysis software, the SPECT imaging data were used to compare rCBF in HD patients and age-matched healthy controls. Thirty-four patients (63%) had MMSE scores ≥28 (non-dementia). Regarding the extent of decreased rCBF in HD patients compared with rCBF in normal control patients, SPECT demonstrated significant rCBF decreases in all patients. rCBF in the perfusion area of the middle cerebral artery was significantly more decreased than in other areas. Multiple logistic regression analysis demonstrated that the presence or absence of a previous history of percutaneous coronary intervention, drug therapy with angiotensin II receptor antagonists and diastolic blood pressure (DBP) were independent risk factors for the extent of decreased rCBF. Regarding the severity of decreased rCBF, stepwise multiple regression analysis indicated that HD duration and systolic blood pressure (mm Hg) were chosen. In conclusion, rCBF decreased in all HD patients studied, irrespective of their clinical symptoms or MMSE scores. Blood pressure was an independent risk factor affecting the extent of decreased rCBF. © 2014 The Japanese Society of Hypertension All rights reserved. Source

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