Engineering controls in veterinary oncology: A survey of 148 ACVIM board‐certified oncologists and environmental surveillance in 20 specialty hospitals

Engineering controls (EC, facility and equipment barriers between hazards and people) are used to avoid exposure to chemotherapy drugs. In this study, American College of Veterinary Internal Medicine board‐certified veterinary oncologists were surveyed about their use of containment primary EC (C‐PEC) and supplemental EC (closed system transfer devices, CSTD). The survey was completed by 148 (38%) of practicing diplomates. All used EC. Both C‐PEC and CSTD were used at 92% of hospitals; however, US Pharmacopoeial Convention Chapter <800> (USP <800>) standards were met at only 19% of hospitals and oncologists did not know the type of C‐PEC at 18% of hospitals. Next, surface contamination and EC use were assessed with environmental surveillance for carboplatin, cyclophosphamide, doxorubicin, and vincristine in 20 veterinary specialty hospitals using a commercially available kit. No contamination with carboplatin, doxorubicin, or vincristine was detected, however, there was contamination with cyclophosphamide at 4 hospitals. Based on this study, most veterinary oncologists use C‐PEC and CSTD, but few meet USP <800> standards. Current measures appear effective for preventing contamination with IV drugs, but additional measures are needed for oral drugs.     

Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome

Persistent Müllerian duct syndrome (PMDS) is a sex‐limited disorder in which males develop portions of the female reproductive tract. Important consequences of PMDS are cryptorchidism and its sequelae of infertility and increased risk of testicular cancer. Anti‐Müllerian hormone (AMH) and its receptor (AMHR2) induce the regression of the Müllerian ducts in male embryos. In Miniature Schnauzer dogs, the genetic basis has been identified as an autosomal recessive nonsense mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the primary objective of this study was to estimate the prevalence of the AMHR2 mutation in North American Miniature Schnauzers, in order to ascertain the value of genetic testing in this breed. An additional objective was to determine whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian Malinois; this would aid development of a genetic test for the Belgian Malinois breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case) was genotyped for the AMHR2 mutation, and DNA from a single PMDS‐affected Belgian Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois was not determined, as no coding or splicing mutations were identified in either AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing Miniature Schnauzers used for breeding or with cryptorchidism.     

Plasma concentrations,behavioural and physiological effects following intravenous and intramuscular detomidine in horses

Reasons for performing study: Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. Objectives: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. Hypothesis: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. Methods: Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 μg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography‐mass spectrometry. Data were summarised as mean ± s.d. for subsequent analysis of variance for repeated measures. Results: Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 ± 71.6 ng/ml vs. 6.9 ± 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 ± 23 cm from the ground 10 min following i.v. detomidine and to 64 ± 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. Conclusions: Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. Potential relevance: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.     

仔泻康口服液药效学和分子机制研究

试验旨在探讨仔泻康口服液治疗仔猪腹泻的药效学和分子机制,为药物的进一步开发提供试验依据。通过小肠推进试验、止泻试验、耳廓肿胀抑制试验、镇痛试验及体外抑菌试验验证仔泻康口服液的药理作用,同时利用网络药理学对仔泻康口服液活性成分进行筛选和靶点预测,并结合生物信息学手段确定仔泻康口服液治疗腹泻的特异性靶点,通过信号通路富集分析探讨其治疗腹泻的分子机制。结果显示,随着剂量的增多,仔泻康口服液抗炎及镇痛效果呈上升趋势,与空白对照组相比差异显著(P<0.05);与空白对照组相比,仔泻康口服液低、中、高剂量组均能显著抑制小鼠小肠碳素墨汁推进距离及推进率,低剂量组差异显著(P<0.05)。仔泻康口服液对大肠杆菌及金黄色葡萄球菌均有抑菌作用,对大肠杆菌效果更明显。本试验利用网络药理学预测了仔泻康口服液的止泻机制,其参与Wnt信号通路,调控细菌侵袭上皮细胞,同时也影响致病性大肠杆菌感染信号等通路;MAPK信号通路通过促进或抑制基因的转录来调控其他炎症介质的生成,同时炎症介质可通过激活MAPK通路和增加细胞表面多种黏附分子的表达促进细胞间黏附和炎症的进展等;NRG/ErbB信号参与神经病理性疼痛的多个方面,在中枢神经系统,主要通过MEK/ERK通路激活小胶质细胞,释放一系列细胞因子和炎性介质,促进神经性疼痛;同时通过调节突触可塑性及中枢去抑制等方式参与神经病理性疼痛;在外周神经系统,NRG/ErbB信号通过调节非髓鞘形成细胞和髓鞘形成施万细胞功能,参与外周神经痛ErbB信号,对镇痛起重要作用等。综上所述,仔泻康口服液可能从肠蠕动、抗炎、镇痛及抑菌4个方面来抑制腹泻。     

Effective plasma alfaxalone concentration to produce immobility in male neutered cats

Objective

To determine the effective plasma alfaxalone concentration for the production of immobility in cats.

卡巴匹林钙的药理作用及其在养殖中的应用展望

目前在肉鸡养殖中没有适宜的解热消炎药,本文介绍了新型解热抗炎药卡巴匹林钙的药理作用及其应用。     

改革兽医药理学实验教学，培养实用型兽医专业人才

兽医药理学实验是一门实践性很强的实验课程,其教学效果直接影响该专业整体教学质量的高低。在药理学实验教学中,从丰富教学内容,提高教学质量;改善教学方法,提高授课水平;增加实践机会,提高实践技能三个方面对兽医药理学实验教学进行改革,为培养实用型兽医专业人才提供保证。     

蚕沙的药理研究及临床应用研究进展

蚕沙既是蚕桑副产物,也是我国传统中药之一,具有抗肿瘤、降血糖、抗氧化等一系列作用。本文对其药理作用及临床应用的国内外研究进展进行了综述,为其进一步研究和开发利用提供了参考。     

重组人粒细胞-巨噬细胞集落刺激因子胶囊的一般药理学试验

为探明由家蚕生物反应器生产的重组人粒细胞巨噬细胞集落刺激因子胶囊的药理作用,以200、400、800μg/kg3种剂量给小鼠灌服,结果对正常小鼠自主活动数与阈下剂量戊巴比妥纳合用对小鼠入睡动物数均无明显影响;以100、200、400μg/kg剂量由十二指肠注入家猫,对家猫的血压、心率、心电图、呼吸频率和深度均无明显影响。     

兽医药理学实验教学改革的探索

兽医药理学实验教学是兽医药理学课程的重要组成部分,为了适应学科发展和社会对兽医人才的需求,广西大学动物科学技术学院在教学过程中对兽医药理学实验教学环节进行了改革和探索,旨在提高兽医药理学实验教学质量和学生的综合素质。     

基于网络药理学探讨白龙散治疗鸡腹泻的作用机制

【目的】采用网络药理学技术与方法预测白龙散治疗鸡腹泻的物质基础、作用靶点和通路。【方法】通过中药系统药理学分析数据库TCMSP筛选中药复方白龙散中的白头翁、黄连、龙胆的有效活性成分及其潜在作用靶点。通过GeneCards和OMIM数据库检索鸡腹泻的相关疾病靶点。利用Venny平台获得药物和疾病的交集靶点。将交集靶点上传至STRING数据库进行分析,构建蛋白互作(PPI)网络图并获得关键靶点,并进一步对关键靶点进行GO功能和KEGG通路富集分析。【结果】共筛选得到活性成分27个,药物靶点57个,疾病靶点4 207个;药物与疾病交集靶点45个。PPI网络发现原癌基因蛋白质C(MYC)、雌激素受体1(ESR1)、白细胞介素-6(IL-6)、G1/S-specific周期蛋白D1(CCND1)等45个蛋白可能是白龙散治疗鸡腹泻的关键靶点。GO功能富集分析确定了112个条目,KEGG通路富集分析确定了22条通路。【结论】中药复方白龙散主要通过槲皮素、山奈酚、异鼠李素等多个化学成分调控转录因子AP-1(JUN)、MYC、ESR1、IL-6等靶点,作用于细胞因子-细胞因子受体相互作用、肿瘤抑制蛋白(...     

动物源食品中呋喃西林及其代谢物氨基脲研究进展

呋喃西林是一种硝基呋喃类抗菌药物,曾被广泛应用于水产养殖过程中。呋喃西林在动物体内的代谢物氨基脲(SEM)会与细胞膜蛋白紧密结合,形成结合态残留物,稳定而长期存在于动物体内,具有致癌、致畸性。本文简要介绍了呋喃西林药物的药理作用及其应用,综述了两种应用于SEM检测的主要方法——高效液相色谱(HPLC)及其联用技术和免疫分析法的研究进展情况及其优缺点,以及食品中的SEM来源,以期对呋喃西林药物及其代谢物SEM有一个较为完整的了解,也为进一步开展相关研究奠定理论基础。     

基于网络药理学和分子对接分析苦参碱抗PRRSV的作用机制

本研究旨在利用网络药理学及分子对接技术从抗炎角度探讨苦参碱抗猪繁殖与呼吸综合征病毒(PRRSV)的作用机制.利用PharmMapper 服务器和Genecards疾病数据库获得苦参碱发挥抗炎作用的潜在靶点;使用STRING在线分析平台结合Cytoscape软件构建靶蛋白相互作用(protein-protein inte...     

淫羊藿药理学研究进展

淫羊藿属植物含有多种有效化学成分,具有广泛的药理作用。淫羊藿多糖通过促进免疫细胞增殖来提高机体免疫力,淫羊藿总黄酮对心血管系统具有保护作用,淫羊藿苷能促进体外软骨生长和软骨细胞增殖,淫羊藿总黄酮对基因表达和细胞凋亡有调节作用。文章综述了近年来国内外淫羊藿药理学研究方面的进展。     

基于网络药理学分析白龙散治疗仔猪腹泻的机制

基于网络药理学预测白龙散治疗仔猪腹泻的活性成分、潜在靶点和相关通路。分析结果显示，白龙散可能通过槲皮素、β-谷甾醇、山奈酚、小檗碱等活性成分作用TNF、MAPK14、VEGFA、IL16、CASP3等关键靶点，调节IL-17等信号通路来调控炎症反应和免疫应答从而发挥治疗仔猪腹泻的作用。     

Pharmacokinetic study of oral amitriptyline in horses

The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (C_max) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (T_max) 1–2 hr, elimination half-life (t_1/2) 17.2 hr, area under plasma concentration–time curve (AUC) 487.4 ng ml⁻¹ hr⁻¹, apparent clearance (Cl/F) 2.6 L hr⁻¹ kg⁻¹, and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.     

Enhanced bioavailability of oral docetaxel by co-administration of cyclosporin A in dogs and rats

Pharmacokinetic and pharmacodynamic endpoints of intravenously and orally administered docetaxel (DT) with or without oral cyclosporine were characterized in rats and dogs. Plasma samples were analysed for DT using liquid chromatography–mass spectrometry. DT area‐under‐the‐concentration–time curve, plasma clearance and maximum serum clearance were significantly affected by cyclosporine in rats (P ≤ 0.0005). Bioavailability of DT alone and DT combined with cyclosporine was 1.3 and 82%, respectively, in rats. In dogs, cyclosporine resulted in a 14–17‐fold increase in peak DT concentrations (P < 0.0005) and area‐under‐the‐curve (P < 0.0005), and a 17‐fold reduction in DT clearance (P < 0.005). Bioavailability of DT alone was 18 ± 16% and statistically exceeded 100% (251 ± 104%) when combined with cyclosporine in dogs. Two of the six dogs receiving DT plus cyclosporine developed neutropenia, and one of the six dogs experienced vomiting and diarrhoea. Cyclosporine significantly alters the disposition of oral DT in dogs and rats, such that clinically relevant serum concentrations are achievable.     

白龙汤的体内抑菌作用研究

采用血清药理学方法,观察白龙汤的体内抑菌作用,并确定白龙汤的最佳采血时间.白龙汤给大耳白兔连续3d灌胃给药,最后一次给药后0.5、1、1.5、2、3、4h取血,制备含药血清,观察对大肠杆菌、志贺氏痢疾杆菌、金黄色葡萄球菌、链球菌的抑菌作用.结果表明:白龙汤含药血清对大肠杆菌、志贺氏痢疾杆菌、金黄色葡萄球菌、链球菌均有抑菌作用,与对照组相比差异极显著P＜0.01,且大肠杆菌、志贺氏痢疾杆菌、链球菌1.5h组与其它各试验组相比差异显著P＜0.05,说明1.5h抑菌作用最强,为给药后最佳采血时间.