Study of the Structure–Activity Relationship of an Anti-Dormant Mycobacterial Substance 3-(Phenethylamino)Demethyl(oxy)aaptamine to Create a Probe Molecule for Detecting Its Target Protein

The current tuberculosis treatment regimen is long and complex, and its failure leads to relapse and emergence of drug resistance. One of the major reasons underlying the extended chemotherapeutic regimen is the ability of Mycobacterium tuberculosis to attain a dormant state. Therefore, the identification of new lead compounds with chemical structures different from those of conventional anti-tuberculosis drugs is essential. The compound 3-(phenethylamino)demethyl(oxy)aaptamine (PDOA, 1), isolated from marine sponge of Aaptos sp., is known as an anti-dormant mycobacterial substance, and has been reported to be effective against the drug resistant strains of M. tuberculosis. However, its target protein still remains unclear. This study aims to clarify the structure–activity relationship of 1 using 15 synthetic analogues, in order to prepare a probe molecule for detecting the target protein of 1. We succeeded in creating the compound 15 with a photoaffinity group that retained antimicrobial activity, which proved to be a suitable probe molecule for identifying the target protein of 1.     

Pharmacokinetics of topically applied ciprofloxacin in tears of mesocephalic and brachycephalic dogs

OBJECTIVE: To evaluate the pharmacokinetics of ophthalmic ciprofloxacin in the tear film of normal mesocephalic and brachycephalic dogs. ANIMALS STUDIED: Twenty mesocephalic dogs and 15 brachycephalic dogs. PROCEDURES: Thirty-five microliters of ciprofloxacin were placed on the cornea of both eyes of each dog. Five brachycephalic dogs were used twice. A tear-test strip placed in the ventral cul de sac for 30 s was used to obtain samples. The tear film of each eye was sampled once at eight time-points post administration, resulting in five samples at each time-point. Samples were evaluated using high performance liquid chromatography. Data from the two skull types were compared using the unpaired two-tailed t-test. RESULTS: The mean concentration of ciprofloxacin in the tears of mesocephalic dogs was 192.8 +/- 269.97, 140.6 +/- 91.06, 56.60 +/- 28.47, 13.6 +/- 6.3, 43.25 +/- 59.71, 16.6 +/- 10.62, 15.6 +/- 13.16 and 6.25 +/- 9.84 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. The mean concentration of ciprofloxacin in the tears of brachycephalic dogs was 272.6 +/- 106.21, 144.4 +/- 142.32, 131.2 +/- 147.07, 75 +/- 80.07, 40.8 +/- 30.35, 35 +/- 21.98, 52.75 +/- 51.87 and 8.6 +/- 12.10 microg/g at 5, 10, 15, 30 min and 1, 2, 4 and 6 h, respectively. There was no statistical difference in tear concentration at any time-point between skull types. CONCLUSIONS: Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h in normal mesocephalic and brachycephalic dogs.     

氨基糖苷类药物抗生素后效应的研究进展

对氨基糖苷类药物抗生素后效应的产生机制、体内外的研究方法、影响因素及常用氨基糖苷类药物抗生素后效应的研究现状进行概述,为评价氨基糖苷类药物的药效学指标和在兽医临床的合理应用提供理论基础。     

兽用喹诺酮类药物发展动态

综述了兽用喹诺酮类药物—包括国内外已上市的、尚在开发中的以及人用药可转化为兽用药三个部分的品种,并对在我国尚未上市的兽用喹诺酮类药物的药理作用及用途作了简介。     

Cephalosporins – pharmacological basis of clinical use in veterinary dermatology

Cephalosporins form a large group of β-lactam antibiotics which are used extensively in human medicine and to a lesser extent in domestic animals. In veterinary dermatology, the principle use for the cephalosporins is the clinical management of canine pyoderma associated with Staphylococcus intermedius . In practice, the use of orally administered first generation cephalosporin drugs to affected dogs is well tolerated and highly efficacious. Bacterial drug resistance appears to occur rarely.     

不同抗生素检测方法检测乳清粉样品结果差异性分析

乳清粉是婴幼儿配方乳粉行业的主要原料之一,对其进行抗生素检测是原料验收的重要参考指标。本研究针对8个批次乳清粉原料,采用4种不同的抗生素检测方法进行了抗生素检测,包括国标法1、国标法2、利普斯50抗生素检测试剂盒法、Charm MRL酶联免疫试剂盒法。不同方法的检测结果存在很大差异,其中国标法1和酶联免疫试剂盒法获得了相同的结果,8个样品均为抗生素阴性。而国标法2及依据此法开发的快速检测试剂盒利普斯50检测则分别显示全阳性和部分阳性的矛盾结果。从上述结果可见,依据国标法2通过嗜热芽孢杆菌检测乳清粉产品抗生素,其结果稳定性欠佳,影响其检测结果可靠性的因素还有待进一步研究。     

30味中药提取物与环丙沙星联用对猪源链球菌体外抑菌作用研究

为筛选与环丙沙星联用对猪源链球菌具有协同抑菌作用的中药提取物,采用试管二倍稀释法测定30味中药醇提物、水提物的最低抑菌浓度（MIC）,采用棋盘稀释法测定30味中药醇提物、水提物与环丙沙星联用对猪源链球菌的部分抑菌浓度（FIC）,采用有机溶剂萃取法初步追踪与环丙沙星联用具有协同抑菌作用的中药萃取物的体外抑菌效果。结果显示,所选30味中药的水提物、醇提物对猪源链球菌均具有一定的抑菌作用,佩兰、黄连、枳壳、郁金等中药醇提物、水提物对猪源链球菌（pf—ce）抑菌活性较强,苍术水提物等对猪源链球菌的抑菌作用较弱;佩兰醇提物与环丙沙星联用对猪源链球菌的协同抑菌作用最强;佩兰醇提物的乙酸乙酯萃取物、氯仿萃取物与环丙沙星联用对猪源链球菌分别具有协同、相加抑菌作用。     

中草药、益生素和抗生素对猪生长性能和免疫功能的影响比较试验

本试验旨在比较中草药、益生素和抗生素对生长猪生产性能和免疫功能的影响。试验选取15kg左右的杜×长×大三元杂交猪90头,随机分为抗生素组、0.2%益生素组和0.2%中草药组,每组3个重复,每个重复10头猪,试验时间28d。结果表明:(1)与抗生素组相比,益生素及中草药组的日增重提高、料重比降低(P>0.05);(2)中草药组的IgG、IgM、IgA、C3、C4含量和益生素组的IgG含量均显著提高(P<0.05)。结论:在生长猪日粮中添加0.2%益生素或中草药能够促进动物生长,提高免疫功能,效果优于抗生素。     

替代抗生素饲料添加剂研究进展

抗生素作为主要的饲料添加剂在几十年的广泛应用过程中造成了致病菌耐药性增强、动物免疫力降低、影响动物疫苗的效价、通过食物链影响人体健康等亟待解决的问题。我国农业农村部已发布公告,自2020年起我国饲料全面禁止添加使用抗生素类添加剂,饲料行业正式进入“无抗时代”。长期以来,研究人员积极寻求研发各种抗生素替代品及绿色无害的饲料添加剂,以消除或减轻禁用抗生素带来的一系列影响。就目前主要抗生素替代品的抗菌特点及抗菌机理进行综述,旨在为“禁抗”后抗菌性添加剂在饲料中的应用提供参考。