Position on zinc delivery to olfactory nerves in intranasal insulin phase I-III clinical trials
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- 作者：A. Hamidovic ahamidovic@salud.unm.edu" class="auth_mail" title="E-mail the corresponding author AHamidovic@salud.unm.edu" class="auth_mail" title="E-mail the corresponding author
- 关键词：Intranasal insulin ; Zinc ; Anosmia
- 刊名：Contemporary Clinical Trials
- 出版年：2015
- 出版时间：November 2015
- 年：2015
- 卷：45
- 期：part_PB
- 页码：277-280
- 全文大小：208 K
文摘
Zinc in pancreatic insulin is essential for processing and action of the peptide, while in commercial preparations zinc promotes hexameric structure and prevents aggregate formation. In 2002, for the first time, insulin was delivered to humans intranasally with resulting cerebrospinal fluid insulin increases, but steady peripheral insulin levels. The novel method of increasing brain insulin levels without changes in the periphery resulted in an expansion of brain insulin research in clinical trials. As pre-clinical research has shown that brain insulin modulates a number functions, including food cravings and eating behavior, learning and memory functions, stress and mood regulation; realization of beneficial effects of insulin in modulating these functions in clinical populations became a possibility with the new direct-to-brain insulin delivery methodology. However, zinc, being integral to insulin structure and function, is neurotoxic, and has resulted in adverse effects to human health. In the last century, intranasal zinc was given preventively during the time of polio outbreak, and in the 21st century intranasal zinc was widely used over the counter to prevent common cold. In both cases, patients experienced partial or complete loss of smell. This paper is the first one to analyze zinc salts and concentrations of those two epidemiological adversities and directly compare formulations distributed to the public with animal toxicity data. The information gained from animal and epidemiological data provides a foundation for the formation of opinion given in this paper regarding safety of intranasal zinc in emerging clinical trials with intranasal insulin.