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Ustekinumab pharmacokinetics after subcutaneous administration in swine model
Tomasz Grabowski,Artur Burmańczuk,Rafał Derlacz,Tadeusz Stefaniak,Anna Rząsa,Jacek Borkowski 대한수의학회 2021 Journal of Veterinary Science Vol.22 No.5
Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.
Development of male sterile transgenic lines in rice by tapetum specific expression of barnase gene
Kumar, Pravin,Kaur, Kulwinder,Purty, Ram Singh,Mohan, Madan,Burma, Pradeep Kumar The Korean Society of Plant Biotechnology 2017 식물생명공학회지 Vol.44 No.4
The key to development of barnase-barstar transgene based hybrid seed technology is the availability of tightly regulated tapetum specific promoter, as any leaky expression of the barnase gene leads to several unintended effects. In the present study, we used two different tapetum specific promoters i.e. promoter of the RTS gene isolated from rice cultivar IR64 and the OsG6b promoter from japonica rice cultivar Hayayuki to express the barnase gene in rice transgenic lines. While viable male sterile transgenic lines could not be obtained with RTS promoter we could develop single copy male sterile lines when the barnase gene was expressed under the OsG6b promoter.
Kumar Paritosh,Amarjeet Kumar Singh,Amita Kush Mehrotra,Deepak Pental,Pradeep Kumar Burma 한국식물생명공학회 2018 Plant biotechnology reports Vol.12 No.6
Anther and tapetum-specific genes are important for understanding male gametophyte development, as well as for their use in the development of barnase/barstar-gene based male sterility and restorer system for hybrid seed production. An essential component of the system is the availability of tapetum-specific promoters. In the present study, anther-specific genes were identified in cotton using microarray-based differential expression analysis, some of which show expression specific to the anthers at a stage where tapetum tissue was fully developed. Validation of the identified genes using RT-PCR and in situ hybridization identified one novel gene (AEG—Anther Expressing Gene) encoding a putative lipid binding protein as having a tapetum-specific expression. Further, three paralogs of the gene were identified in the cotton genome out of which the gene AEG1 (Anther Expressing Gene1) was found to express in the tapetum layer. Analysis of transgenic plants developed in cotton using 1.5 Kb promoter region of the of AEG1 gene fused upstream to the reporter gene β-glucuronidase revealed a broad window of expression of the AEG1 promoter in the tapetum tissue from the tetrad stage of anthers till the degeneration of the tapetum cells. Low levels of expression were also observed in the root tissues. Expression was not observed in the stem and leaves. The broad window of expression of AEG1 promoter in the tapetum tissue makes it a suitable candidate for the expression of the barstar gene for effective fertility restoration in the barnase/barstar system.
Development of male sterile transgenic lines in rice by tapetum specific expression of barnase gene
Pravin Kumar,Kulwinder Kaur,Ram Singh Purty,Madan Mohan,Pradeep Kumar Burma 한국식물생명공학회 2017 JOURNAL OF PLANT BIOTECHNOLOGY Vol.44 No.4
The key to development of barnase-barstar transgene based hybrid seed technology is the availability of tightly regulated tapetum specific promoter, as any leaky expression of the barnase gene leads to several unintended effects. In the present study, we used two different tapetum specific promoters i.e. promoter of the RTS gene isolated from rice cultivar IR64 and the OsG6b promoter from japonica rice cultivar Hayayuki to express the barnase gene in rice transgenic lines. While viable male sterile transgenic lines could not be obtained with RTS promoter we could develop single copy male sterile lines when the barnase gene was expressed under the OsG6b promoter.