新型喜树碱类药性分子的合成与杀螨活性

应用三组分“一锅法”合成了一系列新型喜树碱类药性分子 4a~4n、5a~5n 和 7a~7f ,所有目标化合物均经核磁共振氢谱和质谱确证。室内杀螨活性测定结果表明,所有化合物对朱砂叶螨Tetranychus cinnabarinus均有不同程度的杀螨活性,其中化合物 4l （LC₅₀:25.93 mg/L）和 7d （LC₅₀:28.16 mg/L）的杀螨活性与喜树碱（LC₅₀:24.55 mg/L）的相当。该研究为进一步开展喜树碱作为先导的新农药设计与研究提供了基础。     

Extrapyramidal side effects following subcutaneous metoclopramide injection for the treatment of post operative ileus

Metoclopramide is used for the management of post operative ileus in horses for its gastrointestinal prokinetic effects. Adverse extrapyramidal signs have been reported following its use in horses as well as in man. This report describes the clinical signs exhibited during an adverse reaction suspected to be associated with subcutaneous administration of 0.25 mg/kg bwt metoclopramide at 6 h intervals.     

闽糖92-505的品种特性及遗传组成研究

摘 要：为了更好地了解闽糖92-505的特性,为闽糖92-505大面积示范推广提供技术指导,对闽糖92-505从品种比较试验、福建省预备区域试验到国家区域试验的结果进行分析研究。结果表明：闽糖92-505萌芽率为74.66%,比对照种闽糖70-611高2.07%。分蘖率为109.06%,比闽糖70-611高33.51%。株高为296cm,比闽糖70-611低12cm。茎粗2.560cm,比闽糖70-611低0.013cm。有效茎数为84055条/ hm2,比闽糖70-611多18339条/ hm2,平均蔗茎产量118.424t/ hm2,11-2月份平均蔗糖份15.05%,平均含糖量17.887t/ hm2,比闽糖70-611增产24.30%、蔗糖份提高0.87个百分点,增糖32.20%。闽糖92-505早熟,高产稳产,适应性较广,中抗花叶病、抗黑穗病,抗旱能力中等。遗传组成分析结果表明,闽糖92-505共含有13个不同基础种质,遗传组成丰富。     

阻抗谱法在植物逆境胁迫中的应用研究进展

通过测量植物组织的阻抗参数可以得到与植物生理、病理相关的信息,阻抗谱法提供了一种方便、快捷、无损伤的测量方法,已成为研究逆境条件下植物生理指标变化的有力工具之一.文章对阻抗谱法在水分胁迫、PEG胁迫、植物低温及抗寒性、重金属胁迫、盐胁迫、热胁迫等植物逆境胁迫方面的研究进展进行了综述,为将来培养抗性植物提供依据和参考.     

Successful drug development despite adverse preclinical findings part 2: examples

To illustrate the process of addressing adverse preclinical findings (APFs) as outlined in the first part of this review, a number of cases with unexpected APF in toxicity studies with drug candidates is discussed in this second part. The emphasis is on risk characterization, especially regarding the mode of action (MoA), and risk evaluation regarding relevance for man. While severe APFs such as retinal toxicity may turn out to be of little human relevance, minor findings particularly in early toxicity studies, such as vasculitis, may later pose a real problem. Rodents are imperfect models for endocrine APFs, non-rodents for human cardiac effects. Liver and kidney toxicities are frequent, but they can often be monitored in man and do not necessarily result in early termination of drug candidates. Novel findings such as the unusual lesions in the gastrointestinal tract and the bones presented in this review can be difficult to explain. It will be shown that well known issues such as phospholipidosis and carcinogenicity by agonists of peroxisome proliferator-activated receptors (PPAR) need to be evaluated on a case-by-case basis. The latter is of particular interest because the new PPAR α and dual α/γ agonists resulted in a change of the safety paradigm established with the older PPAR α agonists. General toxicologists and pathologists need some understanding of the principles of genotoxicity and reproductive toxicity testing. Both types of preclinical toxicities are major APF and clinical monitoring is difficult, generally leading to permanent use restrictions.     

A PROSPECTIVE CLINICAL TRIAL COMPARING METRIZAMIDE AND IOHEXOL FOR EQUINE MYELOGRAPHY

A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.     

Identification of allergens responsible for canine cutaneous adverse food reactions to lamb, beef and cow's milk

Lamb, beef and cow's milk are common causes of cutaneous adverse food reactions in dogs. The aim of this study was to identify the proteins responsible for cutaneous adverse reactions to these foods. Ten dogs with allergen-specific serum immunoglobulin (Ig)E to lamb, beef and cow's milk were included in the study. These dogs had been diagnosed with cutaneous adverse food reactions by convincing clinical history and food-elimination diet trials followed by challenge exposure. Sera were analysed by enzyme-linked immunosorbent assay with bovine proteins and SDS-PAGE immunoblots with lamb, beef and cow's milk extracts. All the dogs had specific IgE against bovine IgG, and it was the only protein in the cow's milk extract that bound IgE from the sera studied. In the lamb and beef extracts, the major allergens recognized by the specific IgE of most sera had molecular masses between 51 and 58 kDa, which were identified as phosphoglucomutase and the IgG heavy chain. Other IgE-binding proteins with molecular masses of 27, 31, 33, 37 and 42 kDa were also detected with some sera. Our results indicate that bovine IgG is a major allergen in cow's milk and hence it appears to be a source of cross-reactivity with beef and probably with lamb because of the high homology with ovine immunoglobulins. These results are similar to those found for meat allergy in humans. However, this is the first time that phosphoglucomutase has been identified as an important allergen involved in allergic reactions to lamb and beef.     

酸、铝和盐胁迫对夏季豆科绿肥作物种子萌发及根瘤菌抗氧化酶活性的影响

在逆境土壤,种子的成功萌发与根瘤的形成是确保豆科作物正常生长的关键。本试验选择4种夏季豆科绿肥作物,包括竹豆、绿豆、田菁和豇豆,研究了种子萌发及其根瘤菌抗氧化酶活性(SOD,超氧化物歧化酶;POD,过氧化物酶;CAT,过氧化氢酶;GR,谷胱甘肽还原酶)对逆境胁迫的响应机制。种子萌发设置4个pH水平,即4,5,6,7;4个 NaCl胁迫水平,即0、40、120和200 mmol·L^-1;4个活性铝(Al³⁺)水平,即0、50、100和200 mg·L^-1。根瘤菌培养设置4个pH水平,即4,5,6,7;5个NaCl水平,即0、10、20、30和40 g·L^-1;5个活性铝(Al³⁺)水平,即0、25、50、75和100 μmol·L^-1。结果表明,酸、铝、盐胁迫显著影响几种豆科绿肥作物的种子发芽率及其根瘤菌的抗氧化酶活性,其中根瘤菌抗氧化酶活性较发芽率对胁迫敏感。不同夏季豆科绿肥品种中,田菁不耐酸,但对盐胁迫有一定耐受性;竹豆、绿豆和豇豆对低浓度的盐和弱酸性环境有一定耐受性;但是所有品种对活性铝浓度增加较为敏感。在酸性和盐碱化土壤,较高浓度的H⁺、活性铝或NaCl抑制种子萌发,减缓根瘤菌的生长,降低根瘤菌对有害物质的抗氧化能力,最终限制豆科绿肥作物的早期生长。     

Performance of skin tests with allergens from B. melitensis B115 and rough B. abortus mutants for diagnosing swine brucellosis

Swine brucellosis by Brucella suis biovar 2 is an emerging disease whose control is based on serological testing and culling. However, current serological tests detect antibodies to the O-polysaccharide (O/PS) moiety of Brucella smooth lipopolysaccharide (S-LPS), and thus lack specificity when infections by Yersinia enterocolitica O:9 and other gram-negative bacteria carrying cross-reacting O/PS occur. The skin test with the protein-rich brucellin extract obtained from rough B. melitensis B115 is assumed to be specific for discriminating these false positive serological reactions (FPSR). However, B115 strain, although unable to synthesize S-LPS, accumulates O/PS internally, which could cause diagnostic problems. Since the brucellin skin test has been seldom used in pigs and FPSR are common in these animals, we assessed its performance using cytosoluble protein extracts obtained from B. abortus rough mutants in manBcore or per genes (critical for O/PS biosynthesis) and B. melitensis B115. The diagnostic sensitivity and specificity were determined in B. suis biovar 2 culture positive and brucellosis free sows, and apparent prevalence in sows of unknown individual bacteriological and serological status belonging to B. suis biovar 2 naturally infected herds. Moreover, the specificity in discriminating brucellosis from FPSR was assessed in brucellosis free boars showing FPSR. The skin test with B. abortus ΔmanBcore and B. melitensis B115 allergens performed similarly, and the former one resulted in 100% specificity when testing animals showing FPSR in indirect ELISA, Rose Bengal and complement fixation serological tests. We conclude that O/PS-free genetically defined mutants represent an appropriate alternative to obtain Brucella protein extracts for diagnosing swine brucellosis.     

抗菌药物的合理应用研究进展

自从抗菌药物在医学、兽医临诊实践中被广泛应用以来,已取得良好的疗效。但抗菌药既能发挥防治疾病的有利作用,也会对动物产生损害作用。盲目、滥用抗菌药物带来的危害值得人们关注和反思。抗菌药物的不良反应和滥用抗菌药物的危害,主要表现为细菌产生耐药性、动物体内菌群平衡失调等,其次是药物残留对公共卫生和环境的负面影响。论文强调在了解药动学和药效学原理(峰时间、峰浓度、药时曲线下面积、防突变浓度、抗菌后效应、最小抑菌浓度等)的基础上,指出应该坚持病因学诊断,制定科学的治疗方案,同时要遵守国家相关的法规和条例,做到依法防控疾病。