Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses

The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.     

猪抗病毒精液稀释液应用效果评价

抗病毒精液稀释液在养猪企业实际应用效果表明,抗病毒精液稀释液可使公猪精液在体外恒温有效保存时间延长至6d,精子平均活力达0.7,授配母猪情期受胎率达86％,窝产仔数平均11.2头,仔猪产后死亡率减少13％,猪群健康率平均提高32％.抗病毒精液稀释液与养猪企业原用普通稀释液比较,养猪综合效益提高15％.抗病毒精液稀释液在猪人工授精中应用取得良好效果.     

Topical Ganciclovir Reduces Viral Excretion in Mares With Equine Coital Exanthema

Equid alphaherpesvirus 3 (EHV-3) is the etiological agent of equine coital exanthema (ECE). Because no vaccines or antiviral therapies are available, prevention consists of clinical examination of mares and stallions before mating or semen collection and resting from breeding activities when lesions are present. However, this methodology does not identify subclinically infected animals. Ganciclovir is the most potent compound known to reduce EHV-3 replication. This study aimed to evaluate the efficacy of topical ganciclovir application to reduce EHV-3 replication in experimentally infected mares. A pilot study, after a double-blind completely randomized design, was carried out. Twenty mares were randomly divided into five groups (three treated with ganciclovir with different regimen of doses, one treated with a placebo, and one nontreated). Mares were experimentally infected with EHV-3 on day 0. Rectal temperature, clinical signs, and lesions were recorded. Daily perineal and vaginal swabs were evaluated by quantitative polymerase chain reaction for virus detection. The antibody response was assessed by a virus neutralization test in serum samples collected weekly. Mares experimentally infected with EHV-3 and treated with ganciclovir twice a day for 13 days showed reduced levels and duration of viral excretion and less severe lesions. The viral excretion period was reduced from 18 to nine days compared with the untreated groups. We concluded that ganciclovir had an antiviral effect on EHV-3 replication when topically administered in mares showing clinical signs of ECE. Further trials should be performed to optimize the dose of the antiviral for a definitive formulation.     

自然养殖水体投喂CpG ODN和表面展示VP28的解脂耶罗维亚酵母对凡纳滨对虾(Litopenaeus vannamei)抗WSSV的免疫保护作用

用添加CpG寡聚核苷酸(CpG ODN)和表面展示VP28的解脂耶罗维亚酵母(VP28-yl)的饵料投喂凡纳滨对虾,进行田间中试实验.投喂30 d后进行WSSV感染实验,评估其对凡纳滨对虾的免疫保护作用.投喂实验结束后,CpG ODN投喂组对虾的相对增重率达到(65.8±7.8)% (P＜0.05),这暗示CpG ODN可能具有促生长作用.WSSV攻毒后,CpG ODN和VP28-yl投喂组对虾中WSSV拷贝数与对照组相比均显著降低(P＜0.05),相对免疫保护率分别可达到 26.7%和 36.7%.在投喂结束和WSSV刺激后,CpG ODN组对虾中的呼吸爆发水平均显著升高(P＜0.05).而在VP28-yl投喂组,WSSV引起的细胞凋亡则显著受到抑制(P＜0.05).此外,WSSV刺激后,STAT基因在CpG ODN组和VP28-yl组对虾中的表达水平均显著上调(P＜0.05),分别在第5天和第3天达到最大值,而对照组中则显著下调.研究结果表明,CpG ODN和VP28-yl增强了凡纳滨对虾抗病毒免疫力,对养殖对虾病毒性疫病的防控具有显著作用,可以作为免疫增强剂添加在饵料中,具有在养殖生产中推广使用的前景.     

In vitro antiviral activity of dehydroepiandrosterone and its synthetic derivatives against vesicular stomatitis virus

In this work the antiviral activity of 20 dehydroepiandrosterone (DHEA) analogs with different substituents at positions C-3, C-15, C-16 and C-17 were evaluated against vesicular stomatitis virus (VSV) in Vero cell cultures. The selectivity indexes (SI) obtained with DHEA and epiandrosterone (EA) were 50 and 72.6, respectively. The work showed that the compounds 21-norpregna-5,17(20)-dien-3β,16α-diyl-diacetate, 17,17-ethylendioxyandrostan-5,15-dien-3β-ol and 3β-hydroxypregn-17(20)-en-16-one had higher SI values than ribavirin, which was used as a reference drug. The antiviral mode of action of DHEA was also investigated against VSV replication in Vero cells, and time of addition experiments showed that DHEA mainly affected a late event in the virus growth cycle. Analysis of RNA and protein synthesis indicated that DHEA adversely affected positive strand RNA synthesis and viral mature particle formation.     

青梅果药理学作用研究进展

对青梅果的抗菌作用、抗病毒作用、抗肿瘤作用、代谢调节作用及其他药理学作用近年来的研究成果进行综述,以期为青梅的深入研究和开发利用提供参考。     

重组猪α干扰素理化性状及其体外抗病毒活性研究

[目的]研究重组猪α干扰素（rPoIFN-α）半成品理化性状并对其体外抗病毒活性进行测试与鉴定。[方法]用HEp-2/VSV体系对3批rPoIFN-α蛋白进行抗病毒活性检测,以重组人IFN-α为参比品,测定干扰素效价;用0.25%胰蛋白酶HCl以及鼠抗猪α干扰素单克隆抗体作用已知效价的rPoIFN-α半成品,并检测各批次抗病毒活性,对rPoIFN-α理化性状进行评价;在猪肾细胞株（PK-15）上检测rPoIFN-α对猪细小病毒（PPV）和猪伪狂犬病毒（PRV）的致细胞病变抑制效应,观察rPoIFN-α的体外抗病毒活性。[结果]HEp-2/VSV体系滴定rPoIFN-α半成品效价可达1.5×105IU/ml,比活性达1.1×106IU/mg;rPoIFN-α经0.25%胰蛋白酶37℃作用1h,效价残留率低于1%,经HCl（pH=2.0）处理72h效价残留率高达95%以上,经56℃处理30min效价残留率高于47%,经鼠抗猪α干扰素单克隆抗体37℃作用1h后效价残留率约为1%;体外抗病毒试验表明,用50和500IU/mlrPoIFN-α可分别抑制PRV和PPV对PK-15细胞株致细胞病变效应。[结论]rPoIFN-α具有IFN-α的基本理化性状,其在体外可分别抑制PRV、PPV对PK-15细胞株致细胞病变效应,但剂量有差别。     

Yak interferon-alpha loaded solid lipid nanoparticles for controlled release

To explore the potential of a novel animal interferon formulation for controlled release, the yak interferon-alpha (IFN-α) glutathione S-transferase (GST) fusion protein was expressed in Escherichia coli (E. coli) and the purified recombinant IFN-α was encapsulated into solid lipid nanoparticles (SLN) by double emulsion solvent evaporation (w/o/w) method. The particle size and zeta potential of IFN-α-loaded SLN were 124.2 ± 10.2 nm and −11.2 ± 0.6 mV. The encapsulation efficiency of IFN-α and loading capacity of the SLN were 83.7 ± 4.5% and 1.73 ± 0.15%, respectively. In vitro release study and antiviral assay demonstrated that the IFN-α released from the SLN in a 16-day period exhibited antiviral activity in Madin-Darby bovine kidney (MDBK) cells against vesicular stomatitis virus (VSV), and showed a release pattern of an initial burst release followed by a sustained and slow release. Cytotoxicity assay in cell culture demonstrated that the SLN were not toxic. The results of this exploratory study suggest that the IFN-α-loaded SLN could be a useful formulation for controlled release in veterinary therapeutics.     

大蒜总提取的必要性及其总提取物替抗的优势

文章阐明了大蒜总提取的必要性。大蒜总提取物(TGE)具有的维持动物健康的3大屏障(微生物屏障、免疫屏障以及化学屏障与微生物屏障的双重屏障)作用是其替抗的优势所在。运用猪营养工程技术,是充分发挥TGE替抗优势的根本保证。     

Comprehensive network map of transcriptional activation of chicken type I IFNs and IFN-stimulated genes

Chicken type I interferons (type I IFNs) are key antiviral players of the chicken immune system and mediate the first line of defense against viral pathogens infecting the avian species. Recognition of viral pathogens by specific pattern recognition receptors (PRRs) induce chicken type I IFNs expression followed by their subsequent interaction to IFN receptors and induction of a variety of IFN stimulated antiviral proteins. These antiviral effectors establish the antiviral state in neighboring cells and thus protect the host from infection. Three subtypes of chicken type I IFNs; chIFN-α, chIFN-β, and a recently discovered chIFN-κ have been identified and characterized in chicken. Chicken type I IFNs are activated by various host cell pathways and constitute a major antiviral innate defense in chicken. This review will help to understand the chicken type 1 IFNs, host cellular pathways that are involved in activation of chicken type I IFNs and IFN stimulated antiviral effectors along with the gaps in knowledge which will be important for future investigation. These findings will help us to comprehend the role of chicken type I IFNs and to develop different strategies for controlling viral infection in poultry.