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一种用于阴道内激素递送的自动控释装置。

An automated controlled-release device for intravaginal hormone delivery.

作者信息

Masello M, Ren Y, Erickson D, Giordano J O

机构信息

Department of Animal Science, Cornell University, Ithaca, NY 14853.

Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY 14853.

出版信息

JDS Commun. 2020 Sep 2;1(1):15-20. doi: 10.3168/jdsc.2020-18816. eCollection 2020 Aug.

Abstract

Our objective was to develop and validate an electronically controlled hormone-delivery device for reproductive control of cattle. After development and in vitro testing of a prototype device for intravaginal (IVG) hormone release, we aimed to demonstrate the feasibility of inducing luteal regression by automated treatment with PGF. The IVG device comprises an outer 3D-printed plastic housing, fluid reservoirs connected to delivery pumps and tubing, a programmable circuit board, and a retention mechanism. For in vitro testing, 4 pumps were programmed to release different target volumes (0.1, 0.2, 0.5, 1.0, and 2.0 mL) in 4 replicates (n = 80). A Bland-Altman plot was constructed to assess the magnitude of disagreement between expected and delivered volumes. Observations fell within acceptable limits of agreement (1.96 standard deviations) >95% of the time, indicating overall good agreement (mean difference = -0.005 mL). To assess in vivo performance of the IVG device, lactating Holstein cows with at least 1 corpus luteum ≥15 mm in diameter were randomly allocated to 1 of 3 treatments: (1) IM-PGF (n = 6): two 25-mg intramuscular doses of PGF 24 h apart; (2) DEV-PGF (n = 6): four 25-mg doses of PGF released automatically by the IVG device at 10- or 12-h intervals; and (3) DEV-CTL (n = 4): insertion of an empty IVG device (placebo control). Blood samples were collected at 0, 12, 24, 36, 48, and 72 h after treatment. Data were analyzed by ANOVA with repeated measures. All devices (10/10) remained in situ until removed at 48 h. Progesterone (P4) concentrations from 0 to 72 h were affected by treatment, time, and their interaction. Concentrations of P4 did not differ at time 0 but differed from 24 to 72 h: cows in IM-PGF and DEV-PGF had lesser P4 than cows in DEV-CTL. Conversely, P4 did not differ for IM-PGF and DEV-PGF during the experiment. We conclude that the current IVG hormone-releasing device prototype can be programmed to automatically release PGF for successful induction of luteal regression in lactating dairy cows.

摘要

我们的目标是研发并验证一种用于控制母牛繁殖的电子控制激素输送装置。在研发并对一种用于阴道内(IVG)激素释放的原型装置进行体外测试后,我们旨在证明通过自动注射前列腺素F2α(PGF)诱导黄体退化的可行性。IVG装置包括一个3D打印的外部塑料外壳、连接到输送泵和管道的储液器、一个可编程电路板以及一个固定装置。为了进行体外测试,对4个泵进行编程,使其以4个重复样本(n = 80)释放不同的目标体积(0.1、0.2、0.5、1.0和2.0 mL)。构建了Bland-Altman图以评估预期体积与输送体积之间的差异程度。观察结果在可接受的一致性限度(1.96个标准差)内的时间超过95%,表明总体一致性良好(平均差异 = -0.005 mL)。为了评估IVG装置的体内性能,将至少有一个直径≥15 mm黄体的泌乳荷斯坦奶牛随机分配到3种处理中的一种:(1)肌肉注射PGF(IM-PGF,n = 6):间隔24小时进行两次25 mg的肌肉注射;(2)装置注射PGF(DEV-PGF,n = 6):IVG装置以10或12小时间隔自动释放4次25 mg的PGF;(3)装置对照(DEV-CTL,n = 4):插入一个空的IVG装置(安慰剂对照)。在处理后0、12、24、36、48和72小时采集血样。数据采用重复测量方差分析进行分析。所有装置(10/10)在48小时取出前均保持原位。0至72小时的孕酮(P4)浓度受处理、时间及其交互作用的影响。P4浓度在0时无差异,但在24至72小时有差异:IM-PGF组和DEV-PGF组的奶牛P4浓度低于DEV-CTL组的奶牛。相反,在实验过程中,IM-PGF组和DEV-PGF组的P4浓度无差异。我们得出结论,当前的IVG激素释放装置原型可以进行编程,以自动释放PGF,从而成功诱导泌乳奶牛的黄体退化。

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