Search

Objective: To analyze the clinical manifestation and genetic basis for four children with delayed onset Ornithine transcarbamylase deficiency (OTCD)., Methods: Clinical data of four children with OTCD admitted to the Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2020 to April 2021 were reviewed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Bioinformatic analysis and Sanger sequencing verification were carried out to verify the candidate variants. Impact of the candidate variants on the protein structure was also predicted., Results: The clinical manifestations of the four children included vomiting, convulsion and disturbance of consciousness. WES revealed that the child 1 was heterozygous for a c.421C>T (p.R141X) variant in exon 5, children 2 and 3 were hemizygous for a c.119G>A (p.R40H) variant in exon 2, and child 4 was hemizygous for a c.607T>A (p.S203T) variant in exon 5 of the OTC gene. Among these, the c.607T>A variant was unreported previously and predicted to be pathogenic (PM1+PM2_Supporting+PP3+PP4). Bioinformatic analysis has predicted that the variant may result in breakage of hydrogen bonds and alter the protein structure and function. Sanger sequencing confirmed that the variants in children 2 to 4 have derived from their mothers., Conclusion: The pathogenic variants of the OTC gene probably underlay the delayed OTCD in 4 children. The discovery of the c.607T>A variant has enriched the mutational spectrum of the OTC gene.

Background: Caffeine abundant in coffee has a strong excitation effect on the central nerve system (CNS)., Methods: To combat the adverse effects of sleep deprivation on physical and mental health, this article designed a new nasal temperature-sensitive gel loaded with caffeine, whose effects of awakening and improving cognition in sleep-deprived rats were evaluated., Results: It was found that the caffeine thermo-sensitive in situ gel (TSG) stayed in the nasal cavity for a longer time and increased the contact time between the drugs and the nasal mucosa, which made it possible for caffeine TSG to exert a lasting effect. Secondly, compared with sleep-deprived rats, those administrated with caffeine TSG were more responsive in behavioral experiments. Moreover, the antipentobarbital test proved that caffeine TSG could prolong the sleep latency and shorten the sleep time. Furthermore, caffeine TSG could significantly restore the cognitive ability by ameliorating neuronal cell injuries by upregulating brain-derived neurotrophic factor (BDNF) levels., Conclusion: Generally, caffeine TSG could quickly exert the efficacy of enhancing cognition and wakefulness, and overcome the drawbacks of frequent medications. It can potentially be used for the treatment of psychiatric disorders, such as dementia, Parkinson and Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Electroporation is an important physical technique to improve drug transdermal delivery, although its mechanism remains unclear. Here, some types of polar drugs, including aspirin, diclofenac sodium, metformin hydrochloride, ibuprofen and zidovudine, were used as the model drugs for the exploration of electroporation mechanisms. Electroporation had great influences on the structure of stratum corneum to improve the cumulative permeability due to the formation of pores maintaining for at least 2 h, depending on the power and time, and then the permeation gradually recovered to the normal value after 12 h. A mathematical model was firstly established to exhibit the relationship between the electroporation-improving cumulative permeation and the physiochemical properties of the model drugs, involving oil-water partition coefficient (logP), dissociation constant (pKa) and solubility (S). Increased cumulative permeation depended on increased S, decreased logP and pKa. Electroporation is an effective physical technique to improve transdermal drug delivery depending on itself and the properties of drugs., (Copyright © 2020 Elsevier B.V. All rights reserved.)