地塞米松对肉仔鸡小肠小肽吸收的影响

本试验旨在利用地塞米松构建应激模型,研究应激对肉仔鸡肠道小肽吸收的影响。选取200只21日龄、体质量相近的雄性Arbor Acres(AA)肉仔鸡,随机分为4个处理,每只腹部皮下连续7 d注射1 mL地塞米松磷酸钠注射液(不同处理注射剂量分别为0、0.1、0.52、.5 mg.kg-1BW)。最后一次注射8 h后(15:00)空腹称取体质量,采血、取空肠,进行组织学、皮质酮、小肽Gly-Sar吸收和小肽转运载体PepT-1 mRNA表达的检测,结果表明:⑴地塞米松显著降低肉仔鸡体增质量(P0.05);⑵地塞米松显著抑制肉仔鸡空肠外翻肠囊及刷状缘囊膜对小肽Gly-Sar的吸收(P0.05);⑶地塞米松显著增加肉仔鸡空肠隐窝深度(P0.05),显著降低绒毛高度、吸收面积和绒毛高度/隐窝深度比值(P0.05),对绒毛宽度影响不显著(P0.05);⑷地塞米松显著降低肉仔鸡空肠小肽载体PepT-1 mRNA的表达量(P0.05)。由本试验推测应激可抑制肉仔鸡小肽吸收,产生原因与空肠黏膜形态受损及小肽转运载体PepT-1 mRNA表达量受到抑制有关。     

Myostatin在地塞米松致肌原纤维损伤中的作用研究

为阐明Myostatin在肌原纤维损伤中的作用,并探讨提高畜禽肉产(质)量或控制人类肌肉萎缩的方法,本试验以小鼠为模式动物,采用高剂量地塞米松构建了严重应激模型,研究生理剂量胰岛素对地塞米松致肌原纤维损伤的影响及其与Myostatin基因表达的关系,以及Myostatin基因免疫对地塞米松致肌原纤维损伤的干预作用.结果表明:地塞米松诱导Myostatin基因表达上调及严重的肌原纤维损伤和线粒体肿胀,而胰岛素注射明显减弱了这些效应;Myostatin基因免疫明显抑制了地塞米松对肌原纤维和线粒体的损伤作用.试验结果提示,Myostatin是参与肌原纤维降解的一个关键因子,该作用可能与其刺激了线粒体的功能有关.     

Tissue distribution of dexamethasone in feline ocular structures following single topical application of dexamethasone as an ointment or suspension

Objective To compare the dexamethasone concentration in various structures of the feline eye following a single topical application of dexamethasone as an ophthalmic ointment or suspension. Animals studied Nineteen cats, euthanized due to reasons not related to this study, were selected and their ocular health status evaluated. Selected animals were treated with dexamethasone ointment or suspension. Procedure The concentration of dexamethasone was determined in the following structures of the eye: third eyelid, cornea, aqueous humor, iris, lens, vitreous body, and choroid/retina. The dexamethasone concentration in the eye was measured by radioimmunoassay. The applied amount of dexamethasone was 0.05 mg in 0.05 mL Isopto Dex^® ophthalmic suspension and 0.05 mL Isopto Dex^® ophthalmic ointment, respectively. Cats were treated once with ointment or suspension and were euthanized 3 h or 6 h after treatment. Results At 3 h after topical administration the highest concentrations of dexamethasone were measured in the anterior structures of the eye. The concentrations after application of ointment and suspension were comparable. However, 6 h after administration, the concentrations decreased after administration of suspension and increased further after administration of the ointment, leading to significantly higher concentrations of dexamethasone in the third eyelid, cornea and choroid/retina after treatment with ointment. Conclusion Therapeutically relevant concentrations of dexamethasone after a single topical administration were only achieved in the anterior structures of the eye. Six hours after application there was a substantially higher amount of dexamethasone in the anterior structures of cat eyes treated with ophthalmic ointment compared to ophthalmic suspension.     

Comparison of Three Methods for Evaluation of Equine Insulin Regulation in Horses of Varied Body Condition Score

Multiple dynamic field tests are used for assessment of equine insulin resistance or altered insulin regulation. However, the relationship between markers of glucose homeostasis and insulin disposal obtained by different testing protocols is unknown. We hypothesized that two recently developed field tests for evaluation of equine insulin dysregulation, the insulin response to dexamethasone test (IRDT) and oral sugar test (OST), would yield comparable results to the hyperinsulinemic euglycemic clamp (HEC). Fifteen light breed horses with body condition scores (BCS) 3 of 9 to 8 of 9 were used in this study. Eight horses (BCS, 5 of 9 to 7 of 9) underwent an OST under two different housing conditions, pasture, and stall (experiment 1). These eight horses also underwent an HEC and IRDT over a 4-week period (experiment 2), and results were compared with the OST stall. Finally, eight horses (BCS, 3 of 9 to 8 of 9), including one horse from experiments 1 and 2, underwent an OST on pasture three times over a 14–16-week period during the summer and the fall (experiment 3). The HEC did not correlate with either the OST or IRDT. The OST was not different when performed in the pasture compared within a stall but did change significantly over time on pasture. These results suggest that in insulin-sensitive horses, the OST and IRDT results are not primarily determined by tissue insulin sensitivity in horses of varying BCS. Furthermore, OST results may vary depending on pasture composition or season.     

地塞米松对特发性血小板减少性紫癜外周血淋巴细胞凋亡及Fas/FasL的影响

目的 :观察地塞米松对特发性血小板减少性紫癜 (ITP)外周血淋巴细胞凋亡及 Fas、Fas L表达的影响及其临床意义。方法 :用流式细胞仪检测 30例 ITP患儿治疗前后外周血淋巴细胞凋亡率及 Fas、Fas L蛋白表达。结果 :治疗前淋巴细胞凋亡率及 Fas、Fas L蛋白表达与对照组相比差异无统计学意义 (P>0 .0 5)。治疗后血小板增加时淋巴细胞凋亡率增加 ,Fas、Fas L蛋白表达上调 ,与治疗前相比差异有显著性意义 (P<0 .0 1 )。结论 :地塞米松可显著促进 ITP患儿外周血淋巴细胞的凋亡 ,上调淋巴细胞 Fas、Fas L的表达 ,有助于清除激活的淋巴细胞。     

15-ketodihydro-PGF2 alpha, progesterone and cortisol profiles in heifers after induction of parturition by injection of dexamethasone.

In order to study rapid changes in 15-ketodihydro-PGF2 alpha, cortisol and progesterone in the period preceding parturition in cattle, pre-term parturition was induced in 4 late pregnant heifers. Parturitions were induced by 2 intramuscular injections of 20 mg dexamethasone with a 24-h interval. The first injection was made on days 254, 258, 264 and 265 in gestation, respectively. Twenty-four h before the first injection an intravenous polyurethane cannula was inserted. Blood samples were collected at least every hour until 12 h after parturition and during the second stage of labour at least 6 times per hour. Plasma was analysed for 15-ketodihydro-PGF2 alpha and progesterone by radioimmunoassays, and for cortisol by an ELISA. The average time from injection to parturition was 7.7 (6.6-8.9) days (mean (range)). Two of the heifers had retained foetal membranes (RFM). At the start of the experiment the levels of PGF2 alpha metabolite were low (< 300 pmol/L) and increased slowly to levels between 1000 and 2000 pmol/L at one day before parturition. During the last day, however, the levels increased rapidly and the highest levels (> 10,000 pmol/L) were reached at the time of delivery. No pulsatile release was seen. Immediately after foetal expulsion the PG-metabolite levels decreased rapidly in all animals. In the 2 animals with RFM, however, this decline ceased within a few h. The PG-metabolite levels in these animals then started to increase and reached levels as high as during parturition. Luteolysis occurred between 1.6 and 0.4 days before parturition in all animals. The cortisol profile showed a distinct peak at the time of parturition in the RFM heifers. This peak was absent in the non-RFM heifers. This study shows that the PGF2 alpha release at prepartal luteolysis and parturition is not pulsatile in cattle and that cortisol profiles in heifers with retained foetal membranes might differ from the profiles in non-RFM heifers at the time of parturition.     

地塞米松和左旋咪唑对雏鸡体液免疫应答的影响

分别向免疫期间的各组鸡群给予不同剂量的地塞米松、左旋咪唑后 ,在不同日龄采取血样 ,用血凝抑制 (HI)试验和间接红细胞凝集 (IHA)试验分别对雏鸡新城疫病毒 (NDV)和传染性法氏囊病病毒 (IBDV)抗体滴度进行监测。结果表明 ,小剂量 (0 .1m g/ kg)地塞米松对抗体滴度影响不显著 (P >0 .0 5 ) ,而中 (0 .5 mg/ kg)、高 (1.5 mg/ kg)剂量对抗体的产生有显著的抑制作用 (P <0 .0 1) ;小 (5 mg/ kg)、中 (10 mg/ kg)剂量左旋咪唑对抗体的产生有显著的增强作用 (P <0 .0 1) ,而大剂量 (2 5 mg/ kg)对抗体滴度无显著影响 (P >0 .0 5 ) ;对于因地塞米松造成的免疫抑制 ,小、中剂量左旋咪唑可使抗体滴度恢复至对照组水平 ,甚至对照组水平以上 (P <0 .0 5 ) ,而大剂量左旋咪唑不能逆转由于地塞米松造成的免疫抑制 (P <0 .0 5 )。     

Lack of gender effect on the pharmacokinetics and pharmacodynamics of dexamethasone in the camel after intravenous administration

The pharmacokinetics and pharmacodynamics of dexamethasone were studied in six male and six female camels after a single intravenous dose (0.05 mgkg(-1) body weight) of dexamethasone. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for female and male camels, respectively (mean+/-SEM) were as follows: terminal elimination half-lives were 8.02+/-1.15 and 7.33+/-0.80 h, total body clearances were 95.5+/-16.0 and 124.5+/-11.9 ml h(-1) per kg, volumes of distribution at steady state were 0.72+/-0.08 and 0.87+/-0.14 litre kg(-1), and the volumes of the central compartment were 0.12+/-0.02 and 0.17+/-0.02 litre kg(-1). There was no significant difference in any pharmacokinetic parameter between female and male camels. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol, circulating lymphocytes and neutrophils numbers and were analysed using indirect pharmacokinetic/pharmacodynamic models. The estimated IC50 of dexamethasone for cortisol and lymphocytes for female and male camels were 3.74+/-0.99 and 2.28+/-1.09 and 2.63+/-0.71 and 2.41+/-0.79 ng ml(-1), respectively. The EC50 for neutrophils for female and male camels were 24.5+/-5.83 and 20.2+/-3.82 ng ml(-1), respectively. There was no significant difference in any pharmacodynamic parameter between female and male camels. Dexamethasone in urine could be detected for 4-5 days by enzyme-linked immunosorbent assay and for 3-4 days by liquid chromatography/mass spectrometry after an intravenous dose of 0.05 mg kg(-1) body weight.     

Pharmacokinetics and Pharmacodynamics of Dexamethasone after Intravenous Administration in Camels: Effect of Dose

The pharmacokinetics and pharmacodynamics of dexamethasone were evaluated in healthy camels after single intravenous bolus doses of 0.05, 0.1 and 0.2 mg/kg body weight. Dexamethasone showed dose-independent pharmacokinetics. The pharmacokinetic parameters of the two-compartment pharmacokinetic model for the lowest intravenous dose (mean+/-SD) were as follows: terminal elimination half-life 8.17 +/- 1.79 h; total body clearance 100.7 +/- 52.1 (ml/h)/kg; volume of distribution at steady state 0.95 +/- 0.23 L/kg; and volume of the central compartment 0.22 +/- 0.07 L/kg. The extent of plasma protein binding was linear over the concentration range 5-100 ng/ml and averaged 75% +/- 2%. Pharmacodynamic effects were evaluated by measuring endogenous plasma cortisol concentrations, numbers of circulating lymphocytes and neutrophils and plasma glucose concentrations and were analysed using indirect pharmacokinetic/pharmacodynamic models. The cumulative systemic effect increased with dose for markers of pharmacodynamic activity. The estimated IC50 of dexamethasone for cortisol and lymphocytes for the lowest dose were 3.74 +/- 2.44 and 5.58 +/- 8.37 ng/ml, respectively and the EC50 values for neutrophils and glucose were 45.8 +/- 36.9 and 1.17 +/- 0.71 ng/ml, respectively.     

甲硝唑对地塞米松预处理鸡免疫功能的影响

对地塞米松预处理鸡投以10mg／kg剂量的甲硝唑，观察后者对前者作用的影响。结果表明：地塞米松明显抑制由伴刀豆球蛋白A(ConA)引起的鸡外周血淋巴细胞(PBL)产生IL-2活性，而甲硝唑对这种抑制作用有显著的拮抗作用；地塞米松能抑制鸡对绵羊红细胞(SRBC)悬液和牛血清白蛋白(BSA)两种胸腺依赖性抗原的免疫应答和对布鲁氏菌非胸腺依赖性抗原的抗体应答，但甲硝唑会逆转这种抑制作用；甲硝唑能封闭地塞米松对补体产生的抑制作用。对比实验结果同时表明，在拮抗地塞米松对鸡免疫功能负面影响方面，左旋咪唑与甲硝唑作用非常类似。