荒漠猫血液蛋白质和酶多态性的研究

采用聚丙烯酰胺凝胶电泳法对５只荒漠猫（Ｆｅｌｉｓｂｉｅｔｉ）血液中的血红蛋白（ＨＢ），运铁蛋白（ＴＦ），亲血色蛋白（Ｈｐ）以及乳酸脱氢酶（ＬＤＨ），淀粉酶（ＡＭＹ），酯酶（ＥＳ）和碱性磷酸酶（ＡＬＰ）的多态性进行了研究。结果发现，被检荒漠猫的ＴＦ，Ｈｐ，ＲＢＣ－ＬＤＨ，Ｓ－ＥＳ和Ｓ－ＡＬＰ共５个基因座存在多态性，ＨＢ，ＲＢＣ－ＡＭＹ，Ｓ－ＡＭＹ，Ｓ－ＬＤＨ，ＲＢＣ－ＥＳ和ＲＢＣ－ＡＬＰ共６个基因座为单态，表明荒漠猫的血液蛋白质和酶具有颇大的遗传变异性     

青海细毛羊血红蛋白和红细胞蛋白质多态性的研究

采用聚丙烯酰胺凝胶电泳法对４７９只青海细毛羊的血红蛋白和红细胞蛋白质的多态性进行研究。结果发现：①青海细毛羊的血红蛋白基因座上有ＨＢＡＡ，ＨＢＡＢ，ＨＢＡＣ和ＨＢＢＢ四种基因型。ＨＢ＾Ａ，ＨＢ＾Ｃ等位基因频率分别为０．２６４１，０．７３４９和０．００１０；②血红蛋白基因座的基因型频率和基因频率没有性别间差异；③青海细毛羊ＥＰ－１和ＥＰ－２是单态性蛋白质。     

抗℃型肉毒毒素单克隆抗体的研究

用透村培养法制备的Ｃ型肉毒毒素的类毒素，免疫ＢＡＬＢ／Ｃ小鼠，取其脾细胞与小鼠骨髓瘤细胞系ＳＰ２／０融合。经ＨＡＴ选择培养基选择培养，其细胞融合率平均为７４．５％。用间按ＥＬＩＳＡ法筛选后，共获得９４孔产生抗Ｃ型肉毒毒素抗体的杂交瘤阳性孔。选其中１Ｃ２、１Ｄ１２、１Ｅ８、１Ｇ６、１Ｇ１１、２Ｂ１２、２Ｃ１１、２Ｅ１２、２Ｇ１１、２Ｈ３、３Ａ４、３Ｃ５、３Ｄ３、３Ｆ７、３Ｈ６共１５孔用有限稀释法进行     

羊传染性脓疱弱毒苗对不同病毒株的交互免疫

从国内各地采集到的１１株绵山羊传染性脓疱病毒株经回归动物，羊体毒价测定，细胞培养和电镜观察后，用３批ＨＣＥ细胞弱毒苗分别免疫山羊，２１ｄ后用５０外ＩＤ５０各强毒株分别攻击在两次交互免疫试验中，ＨＣＥ细胞弱毒苗对ＨＣＥ，ＴＣＥ，ＤＰＥ，ＨＢＧ和ＹＬＧＥ毒株保护坚强；对ＨＬＲ，ＬＭＥ，ＨＹＥ和ＬＴＥ毒株保护较好；     

超排山羊卵巢卵母细胞体外成熟和体外受精的研究

以ＴＣＭ１９９＋１０ｍｍｏｌ／ＬＨＥＰＥＳ＋青霉素（６ｍｇ／Ｌ）＋链霉素（５ｍｇ／Ｌ）为基础培养液（ＢＭ），再分别加入不同成分，配成５种卵母细胞成熟液：（Ａ）ＢＭ＋１０％ＥＧＳ；（Ｂ）ＢＭ＋１０％ＥＧＳ＋ＨＣＧ（２．５ｍｇ／Ｌ）；（Ｃ）ＢＭ＋１０％ＥＧＳ＋ＨＣＧ＋Ｅ２（１ｍｇ／Ｌ）；（Ｄ）ＢＭ＋１０％ＦＣＳ＋ＨＣＧ＋Ｅ２；（Ｅ）ＢＭ＋１０％ＥＧＳ＋ＨＣＧ＋Ｅ２＋颗粒细胞（１．５×１０６～３．０×１０６个／ｍＬ）。在３８．５℃、５％ＣＯ２下培养２６ｈ，排卵后第１天卵巢卵母细胞体外成熟率分别为６７．６７％（２０／３０），６０．４２％（２９／４８），８３．６７％（４１／４９）和８０．８２％（５９／７３），排卵后第５天卵巢卵母细胞，在培液Ｄ中体外成熟率为７１．４３％（４５／６３）。排卵后第１天的９８枚卵巢卵母细胞，体外成熟体外受精卵裂率为２１．４３％，２１枚２细胞胚移植５头受体获２头羔羊。研究表明，超排山羊卵巢卵母细胞经体外成熟可获得大量廉价的成熟卵母细胞，并可通过体外受精获得试管山羊     

用反应干扰法检测猪瘟病毒及其抗体

研究出一种检测猪瘟病毒（ＨＣＶ）及其抗体的新方法，首次证实了ＨＣＶ对某些ＨＣＶ株产生的干扰素（ＩＦＮ）有抑制作用。感染ＨＣＶ的猪肾细胞培养物不产生ＩＦＮ，即使加入ＩＦＮ诱生剂也不产生ＩＦＮ，而感染ＨＣＶ的细胞对ＩＦＮ的敏感性不受影响。基于上述结果，建立了一种反向干扰法。此法通过水泡性口炎病毒（ＶＳＶ）产生的ＣＰＥ来检测ＨＣＶ的感染滴度，即在猪肾细胞培养物中，用ＨＣＶ ＧＰＥ＾－株对ＶＳＶ的干扰而产     

青海细毛羊生化遗传多态性的研究

采用聚丙烯酰胺凝胶电泳和火焰光度法对５０９只青海细毛羊细血液和乳汁中ＨＢ，ＥＰ－１，ＥＰ－２，ＫＥ，ＴＦ，ＡＭＹ１，ＡＭＹ２，ＥＳ，ＡＬＰ，ＲＢＣ－ＬＤＨ，Ｈｐα－ＬＡ和β－ＬＧ总共１３个位点的多态性进行了研究。结果为：（１）在青海细毛羊的ＨＢ，ＫＥ，ＴＦ，ＡＭＹ２，ＥＳ，ＡＬＰ，ＲＢＣ－ＬＤＨ１，Ｈｐ，β－ＬＧ总共９个位点上发现多态性，多态性位点的比例为６９．２３％；（２）每个位点实有的平均等位     

塞北兔被毛颜色遗传规律的研究

通过纯繁和测交的方法，分析了塞北兔３种不同被毛颜色的遗传规律，并推断出其基因型：野兔色为ＡＡＢＢＣＣＥＥ和ＡＡＢｂＣＣＥＥ；红色为ＡＡＢＢＣＣｅ；白色为ＡＡＢＢｃｃＥＥ。     

猪瘟兔化弱毒囊膜糖蛋白EI基因的扩增与克隆

本试验直接从细胞培养液中提取猪瘟兔化弱毒（ＨＣＬＶ）ＲＮＡ，并根据猪瘟病毒（ＨＣＶ）Ａｌｆｏｒｔ株和Ｂｒｅｓｃｉａ株的核苷酸序列，将ＥＩ基因分两段，设计并合成了４条引物。采用反转录－多聚酶链式反应（ＲＴ－ＰＣＲ），成功地扩增出了ＨＣＬＶ保护性囊膜糖蛋白ＥＩ基因。以ｐＧＥＭ－Ｔ和ｐＵＣ１９为载体，将ＥＩ基因的两个片段分别进行克隆并转化到大肠杆菌ＪＭ１０１。经过分析鉴定，证明所扩增的片段为ＨＣＬＶＥＩ基因     

有丝分裂原对离体boPBMC增殖和分泌Ig的作用

应用＾３Ｈ－ＴｄＲ掺入法，ＥＬＩＳＡ和ＦＡＣＳ研究了离体奶牛外周血单核细胞（ｂｐＰＢＭＣ）对有丝分裂原的免疫应答。ＰＷＭ和ＣｏｎＡ能不同程度地诱导ｂｏＰＢＭＣ增殖和分泌Ｉｇ；而ＳＥＢ只能使ｂｏＰＢＭＣ高度增殖而不分泌Ｉｇ（Ｐ〉０．０５）。ＰＷＭ诱导的ｂｏＰＢＭＣ经１２ｄ培养，其中ＣＤ４＋／ＣＤ８＋细胞的比率为２．９：１；而ＳＥＢ诱导的细胞为０．３：１。离体ｂｏＰＢＭＣ主要分泌ＩｇＭ和ＩｇＧ１，只有     

Comparing oral and intramuscular administration of medetomidine in cats

Medetomidine (200 μg/kg) was administered orally and, on a seperate occasion, im to 7 cats. Peak serum drug concentrations were reached more slowly after oral (43.6 ± 14.3 min) than after im administration (21.6 ± 10.0 min). The onset of sedation and recumbency lagged after oral administration. There were no statistically significant differences between the 2 routes of administration in peak serum concentrations, systemic drug availability or extent of sedation. However, there was considerable variation in these parameters between individuals after oral administration. The extent of salivation correlated negatively with systemic drug availability after oral administration. Where excessive salivation did not occur, systemic drug availability and the depth of sedation were comparable to, or even higher than, were obtained after the corresponding im administrations. In conclusion, oral administration of medetomidine induced a clinical sedation but, when accurate dosing is a necessity, the oral route may not be very reliable due to possible drug losses through salivation.     

Factors Influencing the Bioavailability of Peroral Formulations of Drugs for Dogs

The oral route is presently the preferred route of drug delivery. Poor oral bioavailability results in variable concentrations of drugs in the plasma and variable pharmacological responses, in addition to higher product costs. The unique canine physiology, anatomy and biochemistry makes designing canine dosage forms a challenging exercise. This article reviews the physicochemical, physiological, pharmacokinetic, pharmacological and formulation factors that can influence the drug availability of the oral formulations in dogs in an effort to provide a source of data to aid development of canine drug products with superior bioavailability.     

五皮口服液对小鼠的利尿作用

研究五皮口服液的利尿作用,通过给水负荷模型小鼠灌服不同剂量的五皮口服液,观察给药后的排尿量,以评价五皮口服液的利尿效果。给药后4 h内,与阴性对照组排尿量1.18 g±0.42 g比较,五皮口服液高、中剂量组(13.5 g生药/kg、6.75 g生药/kg体重)排尿量分别为1.78 g±0.42 g、1.73 g±0.60 g,均极显著增加(P<0.01),低剂量组(3.375 g生药/kg体重)的排尿量为1.34 g±0.91 g,显著增加(P<0.05)。结果表明,五皮口服液具有显著利尿作用。     

利用家蚕蛹生物反应器生产的人粒细胞/巨噬细胞集落刺激因子口服给药的临床前安全性评价

开发了用家蚕蛹表达的人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)的口服药物。试验评价了猕猴、大鼠和小鼠口服rhGM-CSF毒性情况,包括遗传毒性、单剂量和重复剂量的全身毒性以及生殖毒性。毒理学试验显示:静脉给药在NIH小鼠中最大耐受剂量为3 300μg/kg,LD50为2 020μg/kg,在SD大鼠中LD50为3 660μg/kg。在猕猴和大鼠的重复剂量毒性试验结果中显示:口服rhGM-CSF后,除了雌性SD大鼠的血糖含量外,其余各项指标包括白细胞、红细胞、血红蛋白含量、血小板数量以及血细胞凝集等都正常。雌性大鼠每天口服剂量为1 250μg/kg时,给药后血糖浓度显著增加(P<0.001),但在恢复期间可恢复到正常水平。微核实验、CHL染色体畸变试验和埃姆斯测验法都表明无论是在体内还是体外服用rhGM-CSF均未见遗传毒性,普通的生殖毒性试验和围产期及致畸敏感期的毒性试验均未见异常现象,表明口服rhGM-CSF无明显生殖毒性。临床前毒性试验表明口服超过临床剂量10倍的rhGM-CSF与严重的慢性中毒没有联系,其在药理学有效剂量的范围内是很安全的。     

Pharmacokinetics of florfenicol after treatment of pigs with single oral or intramuscular doses or with medicated feed for three days

The pharmacokinetics of florfenicol, a structural analogue of thiamphenicol, were studied in six pigs after single oral and intramuscular doses of 15 mg/kg bodyweight, and after feeding them with medicated feed containing 250 mg/kg for three days, a concentration which provided approximately the same dose rate of the drug. The oral doses contained a specially prepared pelleted formulation of the drug. The bioavailability of the drug was similar for the oral and intramuscular doses. Florfenicol was absorbed rapidly from the feed and its concentration in plasma remained between 2 and 6 microg/ml - above the minimum inhibitory concentration values for common pig pathogens - during the three days.     

Immunogenicity of multiple-epitope antigen gene of HCV carried by novel biodegradable polymers

In order to develop a promising vaccine candidate utilizing a combined approach to induce both antibody production and T-cell activity, the DNA fragment containing MA of HCV with five conserved epitopes was synthesized. Two types of HCV vaccine candidates (the DNA type and DNA/polymers) were constructed using MA. PLA-PEG-PLA and PLGA-PEG-PLGA were synthesized and used as micelles with encapsulated plasmid pcDNA3.1(+)-MA. The preparation of copolymers, the cloning and analysis of recombinant plasmid DNA, in vitro expression, and immunogenicity in transgenic mice were evaluated in detail. The results indicated that even single immunization and oral immunization with DNA/polymers achieved satisfying immune responses in vivo tests. As biodegradable and nontoxic triblock copolymers, the novel copolymers demonstrated a great advantage, as they made long-term and single-immunizing vaccines possible; in addition, the copolymers showed a better adjuvant effect and scarcely any side effects.     

Pharmacokinetics of phenoxymethyl penicillin (penicillin V) in calves

Phenoxymethyl penicillin (penicillin V) was administered intravenously (i.v.) and orally to pre-ruminant calves and the distribution and elimination kinetics, as well as the oral bioavailability, were determined. After i.v. injection, the drug was distributed rapidly in the body, the elimination half-life (t1/2 beta) was 34 min and the apparent volume of distribution at steady-state (Vd ss) was 0.30 l/kg. Mean peak serum drug concentrations were directly related to the oral dose administered, i.e. 0.22 microgram/ml, 1.06 micrograms/ml and 2.14 micrograms/ml after dosing at 10, 20 and 40 mg/kg, respectively. The elimination t1/2 of the drug after oral dosing varied between 90 and 110 min, and the oral bioavailability was approximately 30% of the dose. The co-administration of phenoxymethyl penicillin and probenecid resulted in elevation and prolongation of serum drug concentration. The percentage of drug bound to serum proteins was 78.8% +/- 8.2%. Phenoxymethyl penicillin was probably inactivated and degraded in the gastrointestinal tract of 6-week-old calves fed exclusively hay, silage and concentrates as very low and erratic serum drug concentrations were measured after these calves were dosed orally with the drug at 40 mg/kg. In view of the narrow antibacterial spectrum of the drug and the relatively high dose required, it appears that phenoxymethyl penicillin can only be of limited practical value for the treatment of bacterial infections in preruminant calves.     

党参多糖口服液抗应激及抗炎作用的研究

为研究党参多糖口服液的抗应激与抗炎作用,给小鼠灌服不同剂量（每kg体重灌服9、7、5 g生药）的党参多糖口服液后,通过测定小鼠负重游泳时间、常压耐缺氧时间来评价其应激性作用;观察党参多糖口服液对小鼠耳廓二甲苯致炎的影响,考察其抗炎作用.结果显示,党参多糖口服液能显著（P＜0.01）延长小鼠的游泳时间和常压缺氧条件下的存活时间,对二甲苯所致小鼠耳廓炎症具有不同程度的抑制作用.因此,党参多糖口服液具有抗应激、抗炎作用,该试验可为党参多糖口服液的临床应用提供参考.     

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form.