Influence of Fluid Therapy on Gentamicin Pharmacokinetics in Colic Horses

The aminoglycoside antibiotic gentamicin is commonly used in equine medicine for the prevention and treatment of Gram-negative and staphylococcal bacteria in surgically treated colic patients. The pharmacokinetics of gentamicin in these patients might be altered by the disease status, and/or under the influence of fluid therapy. The purpose of this study was to investigate the effect of intravenous fluid treatment on gentamicin kinetics in colic patients. Colic patients subjected to laparotomy were given fluid infusions according to clinical status. Following gentamicin administration, blood samples were taken for gentamicin analysis at different time points, and the main pharmacokinetic parameters including Vc, Vss, t(1/2) and MRT were calculated. Horses undergoing fluid therapy showed a significantly different t(1/2), clearance and MRT as compared to non-infused patients. However, taking into account the clinical status of the patients receiving fluid support, the data suggest that endotoxaemia, rather than fluid therapy, influence gentamicin pharmacokinetics following laparotomy.     

刺糖对庆大霉素致小鼠肾损伤保护作用的初步研究

本试验旨在应用庆大霉素(GM)诱导建立小鼠亚急性肾损伤的模型,初探维吾尔药刺糖对庆大霉素肾损伤的保护作用。将健康昆明系小鼠28只随机分为7组,分别为A组(125 mg/kg GM)、B组(100 mg/kg GM)、C组(80 mg/kg GM)、D组(125 mg/kg GM+刺糖)、E组(100 mg/kg GM+刺糖)、F组(80 mg/kg GM+刺糖)及G组(对照组),连续用药7 d,于第8天采血后处死,分别测定血液中非蛋白氮(NPN)含量及肾脏、肝脏、脾脏的重量。试验结果显示,D组和F组血液中非蛋白氮(NPN)含量和肾脏系数分别与A组及C组相比差异显著(P<0.05);E组血液中NPN含量与B组相比差异不显著(P>0.05),而E组与B组肾脏系数相比差异显著(P<0.05)。A、B、C 3组对小鼠的肾脏都有不同程度的损伤。试验结果表明,刺糖对125和80 mg/kg GM所致的肾损伤起到了明显的保护作用,但对100 mg/kg GM所致的肾损伤未起到明显的保护作用。     

青蒿琥酯通过Keap1/Nrf2通路抑制氧化应激改善犬急性肾损伤的体内外分析

本研究旨在观察青蒿琥酯对庆大霉素诱导犬急性肾损伤的抗氧化调节作用及其机制。将20只犬随机等分成4组：对照组(Control)、庆大霉素模型组(GM)、青蒿琥酯治疗组(GM+ART)、青蒿琥酯+ML385干预组(GM+ART+ML385)。除对照组,其他组犬采用注射GM建立AKI模型。成功造模后,GM+ART组给与青蒿琥酯,ART+ML385组给与ART和ML385,对照组和GM组给予生理盐水,试验期12 d。用不同浓度GM与MDCK细胞共培养,确定最佳浓度为4.0 mmol·L^-1,用相同方法确定ART最佳浓度为50.0 μmol·L^-1。将体外培养MDCK细胞、过表达Kelch样ECH相关蛋白1(Keap1)的MDCK细胞(M-K)和敲减核因子E2相关因子2(Nrf2)表达的MDCK细胞(M-SiNrf2)分别分成3组：健康对照组、GM对照组和GM+ART干预组,共培养24 h后用于检测。结果显示：1)在动物试验中,GM+ART组肌酐(Cr)、尿素氮(UN)及肾损伤因子1(KIM-1)水平显著低于GM组,GM+ART+ML385组Cr、UN及KIM-1水平显著高于GM+ART组。2)在动物试验中,与GM组比较,GM+ART组Nrf2和谷胱甘肽半胱氨酸连接酶催化亚基(GCLC)蛋白表达上调,Keap1蛋白表达下调,肾组织匀浆中总超氧化物歧化酶(T-SOD)和谷胱甘肽(GSH)水平升高,丙二醛(MDA)水平降低。与GM+ART组比较,给与ML385后Nrf2和GCLC蛋白表达下调,T-SOD和GSH水平降低。3)在细胞试验中,与4.0 mmol·L^-1 GM共培养的MDCK细胞比较,加入50.0 μmol·L^-1ART能显著提高细胞增殖率,降低ROS水平,下调Keap1表达,上调Nrf2、血红素氧合酶1(HO1)及GCLC表达。4)在细胞试验中,与MDCK细胞比较,在GM+ART相同处理下,M-K细胞和M-SiNrf2细胞Keap1蛋白表达上调,Nrf2、HO1及GCLC蛋白表达下调,细胞增殖率降低,ROS含量升高(P＜0.05或P＜0.01)。综上所述,青蒿琥酯对庆大霉素诱导犬急性肾损伤具有保护作用,其作用机制与青蒿琥酯通过Keap1/Nrf2信号通路抑制氧化应激反应有关。     

猫脂肪间充质干细胞及其条件培养基对庆大霉素致损猫肾细胞增殖和凋亡的影响

试验旨在探究猫脂肪间充质干细胞（adipose mesenchymal stem cells,AD-MSCs）及其条件培养基（adipose mesenchymal stem cells conditioned medium,AD-MSCs-CM）对庆大霉素致损的猫肾细胞（crandell rees feline kidney,CRFK）增殖和凋亡的影响及机制。试验分为空白组、庆大霉素（gentamicin,GM）组、AD-MSCs组和AD-MSCs-CM组;用Ⅰ型胶原酶消化法分离猫AD-MSCs,并用流式细胞术鉴定分离的细胞;以0、2、4、8 mmol/L GM完全培养基处理CRFK,并于12、24和48 h用CCK-8法检测细胞活性,筛选最适造模浓度;致损的CRFK分别与猫AD-MSCs及AD-MSCs-CM共培养,于24、48和72 h后用CCK-8法检测细胞增殖活性,24 h后通过Annexin V流式细胞术检测细胞凋亡率,最后通过实时荧光定量PCR检测细胞周期蛋白D1（cyclin d1,CCND1）、细胞增殖核抗原（proliferative nuclear antigen,PCNA）、Bax和Bcl-2基因的表达水平。结果显示,分离培养的猫AD-MSCs在体外培养条件下呈典型的梭型,高表达MSCs表面标记物CD44、CD90和CD105,不表达白细胞表面标记物CD45;AD-MSCs和AD-MSCs-CM均能促进GM致损CRFK的增殖并抑制其凋亡,其中AD-MSCs和AD-MSCs-CM可通过上调增殖相关基因CCND1、PCNA和抗凋亡基因Bcl-2的表达并降低促凋亡基因Bax的表达而发挥促增殖、抑凋亡作用。试验成功分离得到猫AD-MSCs,并证实AD-MSCs及其条件培养基在体外能促进GM致损CRFK的增殖和迁移,为猫AD-MSCs治疗猫急性肾损伤提供依据。     

庆大霉素的毒副作用及其残留检测

就庆大霉素(GM)的作用机理、体内代谢、毒副作用、在动物体内的残留及其检测方法等进行了详尽阐述.     

Effect of gentamicin on CD3+ T-lymphocyte proliferation for treatment of equine recurrent uveitis: An in vitro study

Objective

The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection.

Animals Studied

Three adult horses with no evidence of ophthalmic or systemic disease.

Procedure

Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4′,6-diamidino-2-phenylindole (DAPI) and carboxyfluoroscein succinimidyl ester (CSFE) were used as markers of cell viability and cell proliferation, respectively. Following 5-day culture, live cell counts and CSFE fluorescent intensity data were collected via automated cell count and flow cytometry. The experimental design was duplicated using preservative-free gentamicin and a proprietary brand formulation. Statistical analysis was performed using two-way ANOVA with Tukey's multiple comparison test.

Results

No statistically significant comparisons in CD3+ T-lymphocyte live cell counts and geometric mean fluorescent intensity of CSFE were identified between gentamicin concentrations or formulations.

Conclusions

Gentamicin had no effect on equine peripheral blood CD3+ T-lymphocyte cell viability and proliferation in concentrations ranging from “safe” to “retinotoxic” in relation to intravitreal injection volumes. Low-dose intravitreal gentamicin may not suppress the Th1- and Th17-mediated immune response.