重组胸腺素α1的发酵、纯化及药效研究

为获得重组胸腺素α1 (recombinant thymosin α1,Tα1),采用融合表达方式表达Tα1基因,重组融合表达载体Tα1/pMAL-C2x转化大肠杆菌TB1构建工程菌.对工程菌进行发酵并诱导表达,得到可溶性表达的目的蛋白.亲和层析纯化融合蛋白MBP-Tα1,经凝血酶裂解融合蛋白,Source Q离子交换,得到Tα1单体,最终目的蛋白纯度大于95％.应用犬细小病毒模型进行抗病毒药效学分析显示,重组Tα1具有抗病毒疗效,其药效与阳性药物日达仙相近.     

鲁西黄牛α干扰素基因的原核表达及其抗血清的制备

采用PCR方法从鲁西黄牛基因组DNA中克隆了α干扰素(BoIFN-α)基因,并插入到pET32a+中,构建成重组原核表达质粒pET32a+/BoIFN-α,进行测序和诱导表达.测序结果表明,鲁西黄牛IFN-α基因全长498 个核苷酸,含1个开放阅读框(ORF),编码166 个氨基酸的成熟蛋白,与已报道的牛α干扰素C亚型氨基酸组成同源性为97.6%.表达产物经SDS-PAGE分析,表达出40 ku的融合蛋白,表达量占菌体总蛋白的26.7%.表达产物经镍离子螯合次氨基三乙酸(Ni-NTA)亲和层析纯化,纯化产物进行复性后免疫昆明系小鼠2次,制备高滴度的牛IFN-α抗血清.结果从鲁西黄牛中克隆了IFN-α基因的一种新亚型,即BoIFN-α C2,实现了高效表达和纯化,并制备了鼠抗牛IFN-α,为重组牛干扰素的开发奠定了基础.     

重组胸腺肽α1在大肠杆菌中的表达与免疫活性检测

根据大肠杆菌密码子偏嗜性修改、合成胸腺肽alpha 1（Tα1）基因并连接到pET32α（＋）中构建融合表达载体pET32α-Tα1,转化大肠杆菌BL21（DE3）,IPTG诱导,经15%SDS-PAGE检测,Tα1获得可溶性表达。将诱导表达菌高压均质破碎后进行亲和层析纯化,洗脱蛋白峰经脱盐处理后进行免疫活性测定。通过脾淋巴细胞转化试验测定纯化重组Tα1和人用Tα1的活性,结果显示,重组表达的Tα1具有明显的促进淋巴细胞增殖的活性;脱E受体法E玫瑰花环试验测定结果显示,制备的重组Tα1的E玫瑰花结百分率高于空白对照组14.3%以上（胸腺肽溶液的质量标准为提高10%）,能够明显增强T细胞的活性。     

在大肠杆菌中高效表达具有抗病毒活性的可溶性犬α7干扰素

为了在大肠杆菌表达系统中高效表达具有抗病毒活性的犬0干扰素(CaIFN-α),本研究从犬肝脏中PCR获得CaIFN-α第7亚型(CaIFN-α7)基因,通过重叠延伸PCR方法在CaIFN-α7的N端融合连接内含肽SspDnaB intein (SDI)基因,并将该融合基因连接至pMAL-c2X载体中,构建含有内含肽和麦芽糖结合蛋白基因的CaIFN-α重组质粒.重组质粒在大肠杆菌Rosetta中经IPTG诱导高效表达可溶性CaIFN-α蛋白,经直链淀粉树脂亲和层析纯化后可以得到纯度较高的目的蛋白.重组蛋白经MDCK-CDV检测系统证明具有生物学活性,为该干扰素的大量生产及临床应用奠定了基础.     

α-银环蛇毒素融合基因表达载体的构建及原核表达

设计并人工合成2条引物,对作者构建的重组质粒pMD-α-BGT进行PCR扩增获得α-BGT基因。将目的基因连接至pUCm-T载体构建克隆质粒pUCm-α-BGT。克隆质粒经BamHⅠ、NotⅠ双酶切后连接至融合蛋白表达载体pGEX-4T-1中,成功构建融合基因表达载体pGEX-α-BGT,转化大肠杆菌BL21(DE3)进行IPTG诱导表达。表达产物经15%SDS-PAGE分析,在约34ku处可见明显的外源蛋白质表达带,与预计的分子量大小一致,其表达量约占细菌总蛋白的32.6%。Westernblotting和间接ELISA检测结果表明,α-BGT的融合表达蛋白与天然α-BGT标准品具有相似的抗原性。     

水泡性口炎病毒糖蛋白主要抗原决定区片段基因的原核表达和纯化

参照GenBank中水泡性口炎病毒(Vesicular stomatitis virus,VSV)G蛋白基因的核苷酸序列,设计合成1对特异性引物,采用RT-PCR方法扩增约为810bp的G基因片段,并将其克隆到pGEX-4T-1表达载体上,将经PCR、酶切鉴定以及测序分析正确的阳性重组质粒命名为PGEX-G810,之后将其转化至表达菌株E.coli BL21(DE3),经IPTG进行诱导表达;表达产物经SDS-PAGE、Western blotting等方法进行检测。SDS-PAGE结果表明,重组蛋白主要以包涵体形式存在,相对分子质量约为60 000;包涵体经变性、复性、Glutathione Sepharose 4B亲和层析纯化后,分离得到复性的融合蛋白。纯化的融合蛋白能与VSV阳性血清发生特异性免疫反应,证明表达的目的蛋白具有良好的抗原性。     

驯鹿β-防御素-1(reBD-1)基因的原核表达及蛋白活性的鉴定

旨在构建驯鹿β防御素-1(Reindeerβ-defensin-1,reBD-1)基因的原核表达载体pET-32a(+ )/reBD-1,诱导reBD-1融合蛋白在大肠杆菌中表达,并对其表达产物的生物学活性进行评价.利用RT-PCR技术扩增reBD-1前原肽.从重组克隆载体PMD19T/reBD-1中扩增reBD-1成熟肽编码基因,并克隆入pET-32a(+)中,在大肠杆菌BL21 (DE3)中用IPTG诱导表达reBD-1融合蛋白.表达的融合蛋白扩大培养,进一步纯化后进行体外抑菌试验.结果表明,reBD-1前原肽和成熟肽扩增产物大小分别为215和138 bp,目的基因的序列与驯鹿防御素-1 mRNA序列同源性为100％.前原肽和成熟肽融合蛋白分子量分别为28和24 ku.利用琼脂糖扩散法表明,0.08 mg·mL-1的纯化成熟肽蛋白对金黄色葡萄球菌及大肠杆菌的活性有明显抵抗作用.结果显示,reBD-1前原肽及成熟肽在大肠杆菌中得到了高效表达,其成熟肽对革兰氏阳性菌和阴性菌的活性有抗性.     

布鲁氏菌Omp25的表达及抗原性分析

克隆羊外膜蛋白Omp25基因,在大肠杆菌中表达、纯化,并对Omp25蛋白的抗原性进行分析.以布鲁氏菌染色体DNA模板,扩增Omp25基因,双酶切后克隆至pET32a上,在大肠杆菌ER2566 (DE3)中诱导表达,组氨酸结合树脂柱纯化,Western blotting鉴定Omp25蛋白的免疫原性.将Omp25克隆至载体pET32a,提取的重组质粒经PCR鉴定、双酶切鉴定和测序分析确定目的基因成功插入到了克隆载体中.将重组质粒转化于大肠杆菌ER2566 (DE3)中表达获得HIS融合蛋白,SDS-PAGE分析证明,表达产物为43 000的融合蛋白.Western blotting分析表明,所表达的蛋白具有免疫原性.结果表明,成功地表达并纯化了Omp25蛋白,而且纯化的蛋白具有一定的免疫原性.本试验为进一步研究Omp25蛋白的功能以及寻找布鲁氏菌的诊断性蛋白奠定了基础.     

犬贾第鞭毛虫α-12贾第素基因的原核表达及纯化

为了原核表达、纯化犬贾第鞭毛虫α-12贾第素蛋白,试验经RT-PCR获得α-12贾第素基因片段,克隆至原核表达载体p ET-28a(+),构建重组原核表达质粒p ET-28a-α-12,再转化入E.coli Rosetta(DE3)后,用IPTG诱导表达,表达的重组蛋白经SDS-PAGE和Western-blot分析验证,并用Ni琼脂糖凝胶纯化融合的α-12贾第素蛋白。结果表明:重组原核表达质粒p ET-28a-α-12经双酶切和测序证实构建正确;表达的重组蛋白相对分子质量约为40 ku,且主要以包涵体形式存在;表达量约占菌体总蛋白的15.7%;纯化的重组蛋白纯度达90%以上。     

新孢子虫NcGRA2t基因的原核表达及鉴定

为研究新孢子虫GRA2t基因的原核表达及其表达产物的免疫活性,用EcoRI和XhoI限制性内切酶从pMD20-NcGRA2t上切下NcGRA2t基因,克隆入pGEX-4T1中构建NcGRA2t-GST融合蛋白基因的重组表达载体pGEX-4T1-NcGRA2t。经测序验证后,在大肠杆菌BL-21(DE3)中诱导表达,表达产物采用谷胱甘肽-琼脂糖层析柱进行纯化。用Westernblotting方法,以犬感染新孢子虫Ncl株的血清鉴定表达产物的活性。结果,构建了pGEX-4T1-NcGRA2t原核表达质粒,并在大肠杆菌BL-21(DE3)中诱导表达分子量为46 ku的NcGRA2t-GST融合蛋白,表达产物经谷胱甘肽-琼脂糖层析柱纯化后,得到N端带有GST标签的NcGAR2t蛋白。Westernblotting结果显示,表达产物具有生物学活性。     

白术、微米白术和白术多糖对断奶仔猪生长性能和肠道形态及微生态区系的影响

试验选用96头平均体重14.82 kg左右的杜×长×大断奶仔猪,随机分成4组,每组3栏,每栏8头(公母各半)。对照组饲喂基础日粮,试验1、2、3组分别添加1%80目白术、0.2%白术多糖和1%微米白术。试验期30 d。结果表明:在生长性能方面,与对照组相比,1%微米白术添加组可显著提高日增重(P0.05)、降低饲料增重比和腹泻率,而且效果优于1%80目白术组和0.2%白术多糖组,在肠道形态和肠道微生态区系方面,与对照组相比,日粮添加1%80目白术、0.2%白术多糖、1%微米白术均可不同程度的提高十二指肠和空肠的绒毛高度,加深十二指肠和空肠的隐窝深度,并且增加肠道微生态区系的多样性,其中以1%微米白术添加组的效果最佳。     

Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia

Sissay, M.M., Uggla, A. and Waller, P.J., XXXX. Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia. Tropical Animal Health and Production, XXXX. A 2-year abattoir survey was carried out to determine the prevalence, abundance and seasonal incidence of gastro-intestinal (GI) nematodes and trematodes (flukes) of sheep and goats in the semi-arid zone of eastern Ethiopia. During May 2003 to April 2005, viscera including liver, lungs and GI tracts were collected from 655 sheep and 632 goats slaughtered at 4 abattoirs located in the towns of Haramaya, Harar, Dire Dawa and Jijiga in eastern Ethiopia. All animals were raised in the farming areas located within the community boundaries for each town. Collected materials were transported within 24 h to the parasitology laboratory of Haramaya University for immediate processing. Thirteen species belonging to 9 genera of GI nematodes (Haemonchus contortus, Trichostrongylus axei, T. colubriformis, T. vitrinus, Nematodirus filicollis, N. spathiger, Oesophagostomum columbianum, O. venulosum, Strongyloides papillosus, Bunostomum trigonocephalum, Trichuris ovis, Cooperia curticei and Chabertia ovina), and 4 species belonging to 3 genera of trematodes (Fasciola hepatica, F. gigantica, Paramphistomum {Calicohoron} microbothrium and Dicrocoelium dendriticum) were recorded in both sheep and goats. All animals in this investigation were infected with multiple species to varying degrees. The mean burdens of adult nematodes were generally moderate in both sheep and goats and showed patterns of seasonal abundance that corresponded with the bi-modal annual rainfall pattern, with highest burdens around the middle of the rainy season. In both sheep and goats there were significant differences in the mean worm burdens and abundance of the different nematode species between the four geographic locations, with worm burdens in the Haramaya and Harar areas greater than those observed in the Dire Dawa and Jijiga locations. Similar seasonal variations were also observed in the prevalence of flukes. But there were no significant differences in the prevalence of each fluke species between the four locations. Overall, the results showed that Haemonchus, Trichostrongylus, Nematodirus, Oesophagostomum, Fasciola and Paramphistomum species were the most abundant helminth parasites of sheep and goats in eastern Ethiopia.     

Y‐chromosomal variation of local goat breeds of Turkey close to the domestication centre

Genetic variations in chromosome Y are enabling researchers to identify paternal lineages, which are informative for introgressions and migrations. In this study, the male‐specific region markers, sex‐determining region‐Y (SRY), amelogenin (AMELY) and zinc finger (ZFY) were analysed in seven Turkish native goat breeds, Angora, Kilis, Hair, Honaml?, Norduz, Gürcü and Abaza. A SNP in the ZFY gene defined a new haplotype Y2C. All domestic haplogroups originate from Capra aegagrus, while the finding of Y1A, Y1B, Y2A and Y2C in 32, 4, 126 and 2 Turkish domestic goats, respectively, appears to indicate a predomestic origin of the major haplotypes. The occurrence of four haplotypes in the Hair goat and, in contrast, a frequency of 96% of Y1A in the Kilis breed illustrate that Y‐chromosomal variants have a more breed‐dependent distribution than mitochondrial or autosomal DNA. This probably reflects male founder effects, but a role in adaptation cannot be excluded.     

A brief history of the prevention of infectious diseases by immunisations

Infectious diseases have always been a terrible scourge for humans. The appearance of these plagues, as they were called without distinction, was generally connected to various conditions: asters, climatic changes or religious reasons. The concept of contagious, and then infectious, diseases came slowly. Variolation, i.e. transmission of ‘virulent’ matter to induce a natural disease and the immunity against it, was brought from Constantinople to England by Lady Montague, in 1721. This ‘variolation’ technique was also often performed in veterinary medicine against diseases like sheep-pox or pleuropneumonia. As ‘vaccination’ is the term generally accepted for ‘immunisation’, variolation can be the word designating such a technique. The second period of the history of immunisation began, in 1880, with the studies of Pasteur and his collaborators. A great number of bacterial vaccines were developed: dead, live but attenuated or only parts of pathogens. The viruses were produced in animals, then in eggs and at last, in tissue cultures. Second generation vaccines appeared with genetic engineering: recombinant vaccines, vector vaccines, nucleic acids vaccines, and markers vaccines, among others. These novel technologies can permit the development of new ones and improve the quality of the vaccines already existing.     

Micronutrient Content of Certain Tropical Conventional and Unconventional Feed Resources of Southern India

The ash, silica and certain important micronutrients were estimated in conventional and unconventional feed and fodder resources available in Southern India. Commonly used dry roughages, such as paddy straw, ragi straw, maize kadbi/stalk, jowar kadbi/stalk, bajra stalk and wheat straw, were high in ash (9.9% +/- 0.77%) and silica (6.4% +/- 0.65%) and low in most of the other micronutrients, except iron, with paddy straw containing most silica (>9%). Cultivated non-leguminous (maize, jowar) and improved green crops (hybrid napier, guinea, green panic, NB-21, CO-1) were also high in ash (10.5% +/- 0.60% and 12.5% +/- 0.51%) but were moderate sources of P, Mg and Cu and good sources of Zn (98 +/- 13.8 ppm and 55 +/- 6.7 ppm). Leguminous green fodders (stylosanthus, lucerne, cow pea, soyabean) were excellent sources of Ca (1.9% +/- 0.16%), Mg (0.40% +/- 0.05%), Cu (30 +/- 5.2 ppm), Zn (121 +/- 14.7 ppm) and Fe (1234 +/- 166 ppm) and moderate sources of P. Mixed local grasses and weeds were high in silica (6.9% +/- 1.00%) but were good sources of Cu, Zn and Fe. Cereal grains (maize, wheat, rice, ragi) were low in ash (2.9% +/- 0.33%) and were relatively poor sources of Ca (0.22% +/- 0.03%), Mg (0.19% +/- 0.03%) and Cu (13 +/- 3.1 ppm). Pulses were low to medium sources of most minerals and good sources of Fe (1230 +/- 293 ppm). Oil seed cake/extractions (groundnut cake, cotton seed cake, soyabean meal, sunflower cake, safflower cake) and cereal by-products (rice polish, rice bran, wheat bran) were excellent sources of P (1.1% +/- 0.47% and 2.3% +/- 0.19%) and good sources of Zn (65 +/- 3.9 ppm and 66 +/- 10.7 ppm) and Fe (938 +/- 130 ppm and 662 +/- 126 ppm). Among the unconventional feeds screened, orange peel, sunflower heads, meat meal, rubber seed cake, spirulina algae and sea weeds contained plentiful Ca, Zn and Fe: tree leaves/top feeds (mulberry, erythrina, glyricidia, banana, subabul, groundnut haulms) were excellent sources of Ca (1.5% +/- 0.13%), Zn (120 +/- 22.9 ppm) and Fe (1033 +/- 133 ppm) but relatively poor sources of P. Soyabean husk, cocoa seed husk, rubber seed cake and meat meal were moderate to good sources of P (1.0% and 0.33%). The high Zn and Fe values of most feeds/fodders were probably due to soil contamination. This account of the micronutrient content of feed/fodder resources should help in strategic supplementation intended to alleviate local deficiencies.     

Bovine Mastitis in Selected Areas of Southern Ethiopia

A study on bovine mastitis, designed to determine the causal agents, prevalence of infection and impact of risk factors in three cattle breeds, was conducted in selected areas of southern Ethiopia. A total of 307 lactating and non-lactating cows, of which 162 were indigenous Zebu, 85 Jersey and 60 Holstein-Friesian, were examined by clinical examination and the California mastitis (CMT) test. Of these, 40.4% were positive by CMT and bacteriology for clinical or subclinical mastitis, with prevalence rates of 37.1% and 62.9%, respectively. Out of 1133 quarters examined, 212 (18.7%) were found to be infected, 83 (39.2%) clinically and 129 (60.8%) subclinically. The prevalence of mastitis was significantly higher in Holstein-Friesian than in indigenous Zebu, in non-lactating cows than in lactating cows, in the early lactation stage than in the mid-lactation stage, in cows with lesions and/or tick infestation on skin of udder and/or teats than in cows without this factor, and in the wet season than in the dry season. Mastitis increased with parity number (R = 0.9). Of 248 CMT and clinically positive udder quarter samples analysed microbiologically, 212 were culturally positive for known mastitis pathogens and 36 were negative. Of the 199 positive samples, Staphylococcus accounted for 39.2%, Streptococcus for 23.6%, coliforms for 14.1%, Micrococcus and Bacillus species for 8.0% each and Actinomyces or Arcanobacterium (Corynebacterium) for 7.0%. It was concluded that there was a high prevalence of clinical and subclinical mastitis, mainly caused by Staphylococcus aureus, Streptococcus agalactiae and Escherichia coli, in this study area.     

不同日粮氮水平对山羊氮代谢和微生物蛋白质合成的影响

本试验旨在探讨不同日粮氮水平对内蒙古白绒山羊氮代谢和微生物蛋白质合成(MCP)的影响,以达到提高氮利用率,减少环境污染和饲料资源的浪费。试验选用9只体况良好、体重为(43.83±2.95)kg,装有瘤胃瘘管的内蒙古白绒山羊,按体重随机分为3组,每组3只。日粮分为低氮7.5%、中氮10.5%、高氮13.5%3个氮水平。试验使用常规试验方法分析测定粪尿血液等生化指标,通过全收尿法和尿嘌呤衍生物法估测MCP。结果表明:随着氮水平增加,氨氮(NH3-N)浓度、氮摄入量、尿氮排出、尿中尿素氮(UUN)和MCP显著增加(P0.05),干物质采食量(DMI)显著降低(P0.01);沉积氮占总摄入氮的比例在中氮组最高,MCP在高氮组最高。综上所述,适当降低日粮氮水平可减少粪尿氮排放,提高反刍动物氮利用率。     

Microsporidial keratopathy in two dogs

A microsporidial keratopathy is described in two dogs. Both dogs presented with a unilateral stromal keratopathy characterized by multifocal coalescing opacities, and the diagnosis was made on histopathologic examination of keratectomy specimens. Transmission electron microscopy (TEM) on formalin‐fixed, paraffin‐embedded corneal tissue was performed in one dog, and the morphologic features were consistent with Nosema species infection. Both dogs were initially diagnosed and treated by superficial keratectomy. One dog received additional antifungal medication and underwent a penetrating keratoplasty following local recurrence two years later. No other systemic lesions attributable to the microsporidial infection were identified clinically. The clinical and diagnostic pathology findings, treatment, and follow‐up are discussed.     

优质肉鸡S3系体重与体尺性状指标的主成分分析

为研究地方优质肉鸡S3系体重和体尺性状之间的内在相关性,12周龄时选取同一饲养条件下的150只鸡(公母各半)进行体重和体尺性状等7个指标的测定。结果表明:S3系公鸡的体重、体斜长、龙骨长、胸角均显著高于母鸡(P0.05);公母鸡体重、体斜长、胸宽、胫围这4项指标变异系数较大,有较大选育空间;体重与体斜长、龙骨长、胸宽、胸角、胫围呈极显著正相关(P0.01),相关系数分别为0.57、0.52、0.51、0.49和0.47,与胸深、胫长呈显著相关(P0.05),相关系数分别为0.44和0.39;其他各体尺指标间也存在不同程度的正负相关性(P0.05或P0.01);体重和7个体尺性能指标综合成5个复合指标,累计贡献率达92.6355%,其中第l、2、3、4、5主成分分别解释总变异的36.5353%、22.8642%、13.3115%、10.4535%和8.4710%;各主成分的特征根分布较广,经统计计算入选的5个主成分所包含信息的侧重点各有相同,分别都在一定程度上反映了S3鸡的体型特征和生长发育规律,为今后选育出更加符合市场需求的屠宰加工优质型肉鸡指明了的方向。     

Efficacy of tropicamide,homatropine, cyclopentolate,atropine and hyoscine as mydriatics in Angora goats

Abstract

AIM: To document the efficacy of five commercially available mydriatics for their potential for diagnostic and therapeutic use in Angora goats.

METHODS: Over 8 weeks, the mydriatic effects of 1% tropicamide, 2% homatropine, 1% cyclopentolate, 1% atropine and 0.25% hyoscine were evaluated. Given as block treatments, drugs were applied randomly to one eye of 10 Angora goats, and the contralateral eye served as a control. Vertical and horizontal pupil diameters were measured to document onset ofeffect, time to reach a difference of 5 mm in the vertical/horizontal pupil diameter between eyes, time to maximum pupillary dilation, and duration of mydriatic action.

RESULTS: Onset of mydriasis for all drugs occurred within 15 minutes. Time to reach a difference of 5 mm in the vertical pupil diameter between eyes was shortest for 1% tropicamide and 0.25% hyoscine (0.5 h), then 2% homatropine and 1% atropine (0.75 h), and longest for 1% cyclopentolate (1.5 h). The maximum vertical pupillary dilation occurred earliest with 1% tropicamide and 1% atropine (2 h), followed by 0.25% hyoscine (3 h), 2% homatropine (4 h), and latest with 1% cyclopentolate (8 h). The duration of vertical dilation of the pupil was shortest with 1% tropicamide (6 h), then 2% homatropine (12 h), 1% cyclopentolate (12 h), 1% atropine (24 h), and longest for 0.25% hyoscine (96 h).

The time to reach maximum horizontal dilation of the pupil in treated eyes was shortest with 1% cyclopentolate (1 h), followed by 1% tropicamide (1.5 h), 0.25% hyoscine (3 h), 2% homatropine (3.5 h), and 1% atropine (4 h). The duration of horizontal pupil dilation was shortest with 1% tropicamide (4.5 h), and longest with 0.25% hyoscine (48 h).

CONCLUSION: All five mydriatics induced clinical dilation. Tropicamide (1%) had the shortest duration of effect, but gave incomplete dilation. Good dilation was achieved with 1% cyclopentolate and 2% homatropine, but took too long to reach maximum dilation for routine mydriasis. The largest vertical dilation of the pupil was achieved with 1% atropine and 0.25% hyoscine, but pupils remained dilated for more than 24 h.

CLINICAL RELEVANCE: For routine mydriasis in goats, it is recommended that 1% tropicamide be used, though there may be incomplete dilation. For a longer duration of mydriasis, such as in the treatment of anterior uveitis, 1% atropine or 0.25% hyoscine would be the drugs of choice.