Lysine is one of the limiting AA in the diets of dairy cows and is typically fed as rumen-protected Lys (RPL). We hypothesized that supplementation of RPL during the postpartum period would improve the productive performance in dairy cows. Objectives were to use meta-analytic methods to explore the effects of feeding RPL on performance and blood AA profile in lactating dairy cows. An additional objective was to identify an optimal concentration (%) of Lys in MP (LYSMP) and determine if responses to LYSMP were associated with the concentration (%) of Met in MP (METMP). The literature was systematically reviewed, and 13 experiments, comprising 40 treatment means and 594 lactating cows, were included in the meta-analysis. All experiments had a nonsupplemental control (CON; n = 17 treatment means), or a group supplemented with RPL (n = 23 treatment means). Cows supplemented with RPL were supplied additionally with a mean (±standard deviation) 19.3 ± 10.3 g/d metabolizable Lys (5.1-40.6 g/d). Meta-analytical statistics were used to estimate the weighted mean difference in STATA. Mixed models were fitted to the data to investigate the linear and quadratic effects of LYSMP, METMP, and interactions between LYSMP and METMP. All models included the random effect of experiment and weighting by the inverse of the SE of the means squared. Cows that began receiving RPL in early lactation (≤90 DIM) or for an extended duration (≥70 DIM) produced 1.51 kg/d more milk compared with CON cows. Increasing digestible LYSMP from 6.5% to 8.5% linearly increased yields of milk, FCM, ECM, and milk fat by 1.8, 2.5, 2.4, and 0.10 kg/d, respectively, and tended to increase milk protein yield and body weight gain by 0.07 and 0.09 kg/d, respectively, without a concurrent increase in DMI. Interactions between the linear effects of LYSMP and METMP were observed for FCM/DMI or ECM/DMI. In a diet with low METMP (e.g., 1.82% of MP), a digestible supply of 7.40% LYSMP would result in 1.46 and 1.47 kg/kg FCM/DMI or ECM/DMI, respectively; however, with high digestible METMP (e.g., 2.91% of MP), supplying 7.40% of digestible LYSMP would result in 1.68 and 1.62 kg/kg FCM/DMI or ECM/DMI, respectively. Increasing digestible LYSMP from 6.5% to 8.5% linearly increased blood concentrations of Lys by 16.6 µM, whereas blood concentrations of Met and Ala decreased by 4.6 and 6.0 µM, respectively. Nevertheless, an interaction was also observed between LYSMP and METMP for blood concentrations of total EAA because as METMP increased, the positive response to LYSMP on total EAA was also increased, suggesting a competitive mobilization of AA and their utilization in various body tissues. Only 4 out of the 13 experiments in this meta-analysis involved primiparous cows; thus, insufficient data were available to understand the role of supplemental RPL in primiparous cows. Collectively, feeding RPL improved productive performance, and the increments were maximized up to 9.25% of LYSMP in multiparous dairy cows.

2024-07-01·International Journal of Pharmaceutics

Development of ropivacaine hydrochloride-loaded dissolving microneedles as a local anesthetic agent: A proof-of-concept

Article

作者: Im, Ji Yeon ; Karn, Pankaj Ranjan ; Lee, Kyungmin ; Cho, Dong Youl ; Donnelly, Ryan F ; Hamda, Okto Tri ; Ramadon, Delly ; Aileen, Vania ; Eum, Jae Hong ; Kim, Gwanyoung ; Kim, Da Hye ; Anjani, Qonita Kurnia ; Hwang, Hana ; Kim, Dong Hwan ; Kim, Min-Hwan

Ropivacaine hydrochloride (RPL) is a local anesthetic agent that has been widely used for the treatment of pain during or after surgery. However, this drug is only available in parenteral dosage form and may contribute to the infiltration of RPL into the plasma, causing some undesirable side effects. Intradermal delivery of RPL using dissolving microneedles may become a promising strategy to deliver such drugs into the skin. This research aimed to develop RPL-loaded dissolving microneedles (DMN-RPLs) as a proof of the concept of intradermal delivery of a local anesthetic. The DMN-RPLs were fabricated using either centrifugation or air-pressurized chamber methods. Several polymers, such as poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol) (PVA), and sodium hyaluronate (SH), were utilized for manufacturing the DMN-RPLs. The prepared DMN-RPLs were assessed for their thermal properties, chemical bonds, mechanical strength, insertion ability, skin-dissolution study, and drug content. Furthermore, in-skin deposition and dermatokinetic studies were also performed. The results showed that F9 (30 % w/w PVP-4 % w/w SH) and F10 (30 % w/w PVP-5 % w/w PVA) containing 5 % w/w of RPL were the most promising formulations, as shown by their needle height reduction (<10 %) and insertion depth (∼400 μm). Both formulations were also able to deliver more than 60 % of the RPL contained in the DMNs into the epidermis, dermis, and receiver compartment. This study, for the first time, has provided a proof concept to deliver RPL as a local anesthetic using DMNs and the intradermal route, aiming to minimize pain and discomfort during administration and improve the patient's experience.

2024-04-01·Reproduction in Domestic Animals

Supplementation of rumen‐protected lysine during the close‐up period improves vaginal discharge clearance in Holstein dairy cows

Article

作者: Yamagishi, Norio ; Kusaba, Nobuyuki ; Kawashima, Chiho ; Hayakawa, Hina ; Sugimoto, Yusuke ; Goto, Akira ; Taniguchi, Aki

AbstractWe aimed to evaluate the effects of rumen‐protected lysine (RPL) supplementation during the close‐up period on uterine involution and the resumption of ovarian function in dairy cows. Fifty‐two multiparous Holstein cows were categorized based on parity and expected calving date and randomly assigned to the RPL or control (CON) groups. The RPL group received 80 g of RPL daily from day 21 before the expected calving date until parturition. Blood samples were obtained twice weekly from pre‐supplementation to 6 weeks postpartum. The onset of luteal activity postpartum was determined via ultrasonography twice weekly for up to 6 weeks postpartum. Uterine involution was tracked at 3 and 5 weeks postpartum through the vaginal discharge score, percentage of polymorphonuclear cells (PMN) in endometrial cytology samples, presence of intrauterine fluid, and gravid horn diameter via ultrasonography. Before supplementation, the RPL group showed amino acid imbalance, which was improved by RPL supplementation. There were no significant differences in the onset of luteal activity, percentage of PMN, intrauterine fluid, or the diameter of the uterine horn between the two groups. The vaginal discharge score in the RPL group decreased from 3 to 5 weeks postpartum, whereas that in the CON groups did not decrease. The number of cows with clinical endometritis was lower in the RPL group. Overall, RPL supplementation during the close‐up period enhanced vaginal discharge clearance, potentially averting clinical endometritis, but did not affect the first ovulation in dairy cows.

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适应症	最高研发状态	国家/地区	公司	日期
炎症性肠病	临床2期	瑞典	AstraZeneca PLC	2001-08-01
鼻炎	临床2期	瑞典	AstraZeneca PLC	1999-02-01
哮喘	临床2期	美国	-	-
哮喘	临床2期	-	阿斯利康制药有限公司	-
过敏性鼻炎	临床2期	-	阿斯利康制药有限公司	-
过敏性鼻炎	临床2期	欧洲	AstraZeneca Pharma India Ltd.	-