Pharmacokinetic behavior in sheep and cattle of 5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1H-benzimidazole, a new fasciolicide agent

The physicochemical properties, p K _a, Log P and solubility of compound alpha, (5-chloro-2-(methylthio)-6-(1-naphthyloxy)-1 H -benzimidazole), a new fasciolicide agent, were characterized using conventional methods. Also, its pharmacokinetics was evaluated in sheep and cattle. In both species an oral dose of 12 mg/kg was administered. Blood samples were collected during 144 h and analyzed by using an HPLC assay. Results showed that compound alpha is a weak base with a p K _a value of 2.87 and log P of 1.44. The solubility was very low in aqueous solvents. Pharmacokinetic studies showed that in both species compound alpha could not be detected at any sampling time. The mean half-life ( t _½) values of alpha sulphoxide in sheep and cattle were 19.86 and 29.87 h, while the half-life values of alpha sulphone were 19.43 and 46.32 h respectively. C _max values of alpha sulphoxide did not differ between species while alpha sulphone values were higher in cattle. Plasma protein binding of alpha sulphoxide was between 82% and 86%. These results, combined with the previous efficacy studies, suggest that compound alpha could be a promising fasciolicide agent.     

Anticoccidial activity of 9-(2-chloro-6-fluorobenzyl)-6-methylaminopurine and 9-(2-chloro-6-fluorobenzyl)-6-dimethylaminopurine against Eimeria tenella, E. acervulina, and E. maxima in battery trials

In a series of battery experiments utilizing 9-day-old White Leghorn male chicks, 9-(2-chloro-6-fluorobenzyl)-6-methylaminopurine (VM 6387) and 9-(2-chloro-6-fluorobenzyl)-6-dimethylaminopurine (VM 6736) showed remarkable anticoccidial activity against Eimeria tenella, E. acervulina, and E. maxima. The effective dose range was estimated from the results of the efficacy test against E. tenella on the basis of improvement of body weight gain and clinical signs of infection. The tests included dietary levels of 60-100 ppm of VM 6387 and 70-110 ppm of VM 6736. Both compounds gave good protection against E. acervulina and E. maxima at the same dose range. The sporulation of oocysts obtained from cecal contents of birds fed lower levels of VM 6387 was inhibited. Studies of the effects of VM 6387 on stages of the E. tenella life cycle demonstrated that the compound possesses remarkable activity at 1-5 days post-infection corresponding to the period of schizogony, as well as prolonged activity thereafter, when the parasite was undergoing gametogenesis.     

Expression of insulin-like growth factor binding protein (IGFBP)-3, and the effects of IGFBP-2 and -3 in the bovine corpus luteum.

The present study was conducted to gain insight into the insulin-like growth factor (IGF) system in the bovine corpus luteum (CL). Specific aims were to measure the levels of IGF binding protein-3 (IGFBP-3) and RNA encoding IGFBP-3 in the CL throughout diestrus, and to investigate the effects of IGFBP-2 and -3 on IGF-I-stimulated progesterone (P4) production and IGF-I-receptor binding. Bovine CL were collected from a local abattoir and classified according to stage of diestrus based on anatomical characteristics. Corpora lutea from early, mid and late diestrus were each analyzed for the presence of IGFBP-3 by ligand blot analysis, and for RNA encoding IGFBP-3 by Northern blot analysis. Dissociated cells from mid-cycle CL were treated with IGF-I, IGFBP-2 or -3, or a combination of IGF-I and IGFBP-2 or -3. The effect of IGFBP-2 and IGFBP-3 on [(125)I] IGF-I binding to its receptor on CL plasma membranes also was investigated. IGFBP-3 protein and RNA expression were higher in early CL, compared to mid or late CL (p < 0.05). IGF-I stimulated P4 production in a dose-dependant manner (p < 0.05). IGFBP-2 and -3 blocked the stimulatory effect of IGF-I on P4 production (p < 0.05). Both IGFBP-2 and -3 inhibited [(125)I]-IGF-I binding to its receptor in a dose-dependant manner. These results demonstrate that IGFBP-3 protein and RNA are expressed predominantly during early diestrus in the bovine CL. Moreover, both IGFBP-2 and -3 can modulate IGF-I actions in the CL by interfering with binding of IGF-I to its receptor.     

A Case of Olfactory Neuroblastoma Induced in A Rat by N-Nitrosobis(2-hydroxypropyl)amine

N-nitrosobis(2-hydroxypropyl)amine (BHP) is a well-known carcinogen and induces tumors in various tissues. In the present paper, a case of olfactory neuroblastoma (ONB) induced in a rat by BHP is described. The tumor was observed in one out of 25 male rats that received 2000 ppm of BHP in drinking water from 6 to 18 weeks of age and were sacrificed at 26 weeks of age. Histologically, the tumor arose in the posterior nasal cavity and consisted of small round cells and elongate cells with scant basophilic cytoplasm. The neoplastic cells proliferated with compartmentalization into the lobules by fibrovascular septa. True rosettes, pseudorosettes and an intercellular fibrillar matrix were occasionally observed. Immunohistochemically, the tumor cells were positive for NF120/200 and β III-tubulin. These results indicate that the present tumor is the first case of ONB induced in a rat by BHP treatment.     

重磁方法在红井子地区C5-3航磁异常查证中的应用

以C5-3航磁异常的基本特征为依据,结合区域地质情况,推断航磁异常的成因。通过地面高精度磁测和重力测量方法对航磁异常进行了查证。在异常解释过程中利用了地面高精度磁测和重力测量数据进行2.5D重磁联合反演,对C5-3异常进行定性到定量的解释,指导验证钻孔的布设并最终查明航磁异常的成因。     

3-甲基-2-[3-(2-呋喃基)丙烯甲酰]-喹喔啉- 1,4-二氮氧化物合成研究

为改善3-甲基-2-[3-(2-呋喃基)丙烯甲酰]-喹喔啉-1,4-二氮氧化物的制备工艺,寻找一种与喹烯酮结构相似,但药效更好、毒性更低的喹喔啉类兽药,参考喹烯酮的制备工艺,对苯并呋咱-N-氧化物环氧化反应条件,乙酰甲喹制备工艺,目标物制备条件进行了研究。试验用25%氨水作为催化剂,优化了催化剂用量,缩短了反应时间,提高了目标物产率,使目标物产率达到88.95%。合成的产物理化性质和光谱分析证明系为所合成的目标物。     

胰岛素样生长因子结合蛋白3和胰岛素样生长因子结合蛋白5基因在内蒙古白绒山羊皮肤中的表达研究

本研究旨在探明胰岛素样生长因子结合蛋白(insulin-like growth factor-binding protein,IGFBP)在内蒙古白绒山羊绒毛发育的不同生长阶段皮肤组织中的表达变化情况。试验采用实时荧光定量PCR技术,对内蒙古白绒山羊绒毛生长发育的各个时期皮肤中IGFBP-1~IGFBP-6基因的表达进行了测定,并通过埋植褪黑素组改变绒毛生长周期的研究,来鉴定IGFBP-1~IGFBP-6基因中高表达的结合蛋白的作用。结果表明,IGFBP-3和IGFBP-5在绒山羊绒毛生长发育的各个时期的皮肤组织中均有表达,但是IGFBP-5的表达相对于IGFBP-3的表达具有很强的规律性。结果提示,在内蒙古白绒山羊的绒毛发育过程中,IGFBP-5可能是一个主要的调控因子。     

Evaluation of the effects of intramuscular injection volume on midazolam-butorphanol induced sedation in domestic pigeons (Columba livia)

BackgroundCombinations of midazolam and butorphanol are commonly used in avian sedation protocols but no studies have been performed in Columbiformes. Minimizing intramuscular drug injection volumes is desirable, in order to reduce the potential for injection-induced discomfort. Reduction of drug injection volumes can be achieved by using higher concentrated drug formulations. The goals of this study were to evaluate a midazolam-butorphanol sedation protocol in domestic pigeons and to evaluate if a difference in total drug injection volume has an effect on sedation parameters in this species.MethodsTwelve adult pigeons were sedated with butorphanol (2 mg/kg) combined with 4 mg/kg of midazolam as either a standard (5 mg/mL) or concentrated (50 mg/mL) formulation, intramuscularly, in a randomized, blinded, complete cross-over study. Various parameters were used to assess for differences in sedation onset, depth, and recovery. Flumazenil (0.05 mg/kg) was administered intramuscularly for reversal of midazolam 30 minutes after sedative administration.ResultsThe sedation protocol resulted in moderate sedation and all birds became sternally recumbent, while 4of 12 birds lost righting reflex. Recovery was rapid in all birds following administration of flumazenil and no adverse reactions were observed. Significant differences in drug injection volumes had no clinically relevant effects on sedation parameters.Conclusions and clinical relevanceUse of concentrated midazolam resulted in ∼3.5 times smaller total injection volumes, while achieving the same efficacy as standard concentration of midazolam. The reduced injection volumes are desirable from an animal welfare standpoint, as they may reduce the risk of local discomfort associated with intramuscular injections.     

An outbreak of encephalitis in pigeons (Columba livia) in the Canary Islands (Spain)

An encephalitic disease in pigeons, characterized by paralysis of extremities, torticollis, head tremor, and diarrhea, is described. The negative titers in the hemagglutination tests, the presence of Feulgen-positive intranuclear inclusions in the cells of the granular layer of the cerebellum and the fibroblast culture, and the presence of viral particles with an icosahedral-herpetic morphology and a diameter of 100-170 nm all indicate that the etiology of this outbreak may be related to the encephalitis caused by herpesvirus, at present diagnosed only in Iraq and some African countries.     

Identification of a soluble UDP-Gal: Gal (beta 1-4)Glc (or GlcNAc) (alpha 1-3) galactosyltransferase of bovine colostrum

A soluble UDP-Gal: Gal (alpha 1-3) galactosyltransferase was first detected in bovine colostrum and this enzyme activity was simply assayed by using rho-nitrophenyl-beta-lactoside (Gal(beta 1-4)Glc-C6H5NO2, rho NP-lactoside) as an acceptor. Treating the radioactive product with alpha- or beta-galactosidase, the radioactivity (greater than 95%) was released by only alpha-galactosidase and was identified as [3H]galactose. This shows that galactosyl residue was alpha-linked to rho-nitrophenyl-beta-lactoside. Methylation, hydrolysis, thin layer chromatography and fluorography of the reaction product (Gal(alpha 1-)-[3H]Gal(beta 1-4)Glc-rho NP) yielded 2,4,6-tri-O-methyl[3H]galactose, indicating that galactosyl residue had been transferred to the carbon-3 position of the terminal nonreducing beta-galactosyl residue in rho-nitrophenyl-beta-lactoside. These results confirmed that the structure of the reaction product was Gal(alpha 1-3)Gal(beta 1-4)Glc-rho NP. The enzyme requires Mn2+ for its activity, and shows pH optimum from 6.5 to 7.5. rho-Nitrophenyl-beta-lactoside and asialo alpha 1-acid glycoprotein were more effective as an acceptor than N-acetyllactosamine. The bovine colostrum (alpha 1-3) galactosyltransferase could not convert human O red cells into B active cells, indicating that this enzyme preparation did not contain the activity to synthesize human blood group B erythrocytes.     

Sequencing of canine 5-hydroxytriptamine receptor (5-HTR) 1B, 2A, 2C genes and identification of polymorphisms in the 5-HTR1B gene

Polymorphisms of human genes encoding 5-hydroxytriptamine (serotonin) receptors (5-HTRs) are thought to be associated with psychiatric disorders and behavioral traits. In the present study, we searched for corresponding polymorphisms in the dog and compared allelic frequencies for the canine 5-HTR1B, 5-HTR2A, and 5-HTR2C genes among five canine breeds. The canine genes consisted of the following: 5-HTR1B, 1170 bp; 5-HTR2A, 1413 bp; and 5-HTR2C, 1377 bp. All of these genes were highly homologous with the human genes. We found six single nucleotide polymorphisms (SNPs) in the 5-HTR1B gene (G57A, A157C, G246A, C660G, T955C, and G1146C). Genotyping of the respective SNPs revealed that there were inter-breed variations in the genotypes and allelic frequencies for four out of the six identified SNPs, suggesting that further analyses of the polymorphisms of the 5-HTR1B gene would be useful in order to gain an understanding of the genetic background underlying the diversified behavioral traits among canine species.