Place de l'immunostimulation dans la therapeutique anti-infectieuse

An increasing number of substances is capable of potentiating immune responses. These can be grouped into several categories: bacterial products, leucocyte extracts (transfer factor, interferon) thymic hormones and synthetic drugs (levamisole). Their therapeutic use against infections is still uncommon for several reasons. First, the immunostimulants, particularly the bacterial extracts have many toxic side-effects. Second, most of them have not been obtained under pure and chemically-characterized form. Third the mechanisms of immunostimulation are not completely understood and depending on the route and the timing of injection, the immunostimulants can exhibit suppressive activities. For these reasons a larger use of immunostimulant substances requires purified or synthetic materials, careful experimental and clinical analysis of their effects and rigorous indications. These conditions are already fulfilled for some immunostimulants especially in immunodeficient virus-infected patients.     

Bovine Normal and Abnormal Reproductive and Endocrine Functions during the Postpartum Period: A Review

The results of numerous studies on postpartum uterine involution, ovarian activity and endocrinological changes before, during and after normal and abnormal parturitions, have been reviewed in this article. Most studies have shown that abnormal parturition is the main factor which delays completion of uterine involution and occurrence of the first estrous cycle post partum. The reviewed reports also indicated that any interference (corticosteroid injection, overiectomy, etc.) with normal synchronized hormonal changes of parturition can increase the incidence of retained fetal membrane. Reports on the use of hormonal treatments and their effects on the elimination of bacterial infection, rate of uterine involution and the resumption of ovulation activity are conflicting. It is suggested that the use of natural substances such as lipopolysaccharide of E. coli, serum or hyperimmune serum, extracts of poly morphonuclear leucocytes and/or macrophage-granulocyte Colony Stimulating Factor as treatments of postpartum uterine infection may play an important role in the completion of uterine involution and the commencement of estrous cycle .     

免疫增强剂在对虾生产中的研究与应用现状

免疫增强剂是指能够通过提高机体的非特异性免疫功能来增强其抗应激和对病原体的抵抗能力的物质。研究表明,对虾的酚氧化酶原激活系统可被免疫增强剂激活,在激活过程中产生一系列活性物质,通过多种形式参与宿主防御反应,在对虾的免疫识别、防卫及细胞信息传递中发挥着重要作用。免疫增强剂具有作用广泛、特性稳定、安全高效、适宜于作为饲料添加剂来替代抗生素等特点,目前在对虾广泛应用的免疫增强剂主要有免疫多糖类、益生菌、草药提取物、营养因子类物质和生物活性物质等五大种类,文章对它们的作用机理及其应用发展趋势进行了阐述。     

Action of immunostimulants on phagocytosis and derivative actions

One of the main objectives of immunopotentiators is their ability to enhance or to restore natural anti-infectious resistance of normal or immunocompromised hosts. Numerous experimental resistance models have been used in screening such potentiators. However, once such a substance has been selected, its potential and practical use will directly depend on the knowledge of the underlying resistance mechanisms induced, defining its cellular or molecular targets. Phagocytosis-polymorphonuclear or monocyte-macrophage dependent--is the most frequently described variable which have been analysed among the various potentially active mechanisms of non-specific resistance. Various in vivo and in vitro tests might be used and the target of several immunostimulants among the different steps of phagocytosis are described. However, numerous intrinsic limitations are associated with such tests and news models or tests are presented and discussed in order to gain more insights into the evaluation of active substances.     

What can one expect of immunostimulants in the clinical setting?

There exist many potential clinical indications of immunostimulants. Experimental models have elicited great hopes that have not always been confirmed by the preliminary clinical trials, too often performed with minor products. One may hope that new agents under study will allow to extend the use of immunostimulants in immunodeficiency diseases, infections, autoimmune diseases, atopy and cancers.     

Substances derived from 4-ethyl octanoic acid account for primer pheromone activity for the "male effect" in goats

A major constituent of the characteristic "goaty odor" 4-ethyl octanoic acid (4EOA) was previously shown to have no primer pheromone activity. This was also confirmed by our own bioassay system utilizing the recording technique of neural activity of the hypothalamic gonadotropin-releasing hormone pulse generator in goats. However, when the synthetic 4EOA solution was kept at room temperature for several months, primer pheromone activity appeared in the same solution. Headspace gas chromatography/mass spectrometry analysis revealed that there were several newly formed substances in addition to 4EOA samples with primer pheromone activity. These results suggest that 4EOA derived substance(s) but not 4EOA itself is(are) primer pheromone in goats.     

肥大细胞在机体防御反应中的作用

肥大细胞的研究主要集中在过敏性痰病中,肥大细胞在机体抵御病原体感染中发挥着重要作用.肥大细胞除具有识别、吞噬并杀灭病原微生物的功能外,尚能加工、递呈抗原和调节免疫反应.肥大细胞有针对病原信号的特异性受体系统和介质.深入阐明肥大细胞在细菌和病毒感染中的作用和机制,不仅为天然免疫的研究开辟一个新领域,而且对感染性疾病的防治也有重要意义.     

植物提取物的生物学功能及其在仔猪生产上的应用

植物提取物（PE）是通过物理化学等方式从植物中得到的单一或混合物质，含有多酚、生物碱、多糖、精油等活性物质。其生物学功能多样：调控抗氧化酶活，降低过氧化物含量，抑制或清除自由基等；通过调控NF-κB、ERK、JNK活化及相关转录因子的表达，实现机体免疫应答；降低炎性因子及其相关基因表达，缓解炎症；具有抗菌作用，不容易产生耐药性；通过改变癌细胞细胞周期，实现细胞凋亡，达到抗癌目的；对疟原虫、丝虫、克氏锥虫等寄生虫有显著抑制作用。植物提取物在仔猪生产上应用广泛，具有良好的效果：能提高仔猪平均日增重（ADG）、饲料转化率等生长性能，如菠萝茎、八角提取物；促进仔猪消化吸收，提高营养物质代谢；降低血液转氨酶、碱性磷酸酶（AKP）活性，缓解应激；提高仔猪血液抗氧化酶活性，降低过氧化物水平；提高仔猪血液细胞因子、免疫球蛋白的含量，增强机体免疫功能；调控肠道菌群，改善肠道黏膜形态，减少仔猪腹泻。植物提取物是绿色健康的添加剂，其广泛普及可大幅度减少抗生素的使用。随着生物技术的发展，植物提取物在健康养殖中将发挥越来越大的作用。     

生姜黄酮粗提液对部分家蚕病原细菌的抑杀效果试验

采用天然植物活性成分防治家蚕细菌病不仅具有安全、环保的特点,而且还能解决病原菌的耐药性问题。生姜中富含的黄酮类物质具有多种生物活性及药理作用。采用滤纸片法和打孔法研究了生姜黄酮粗提液对家蚕病原细菌卒倒杆菌(Bacillus thuringiensis)和青头败血病菌(Aeromonas)的体外抑菌效果,结果表明7.46、3.73、2.49、1.49和1.07 mg/mL生姜黄酮粗提液对2种家蚕病原细菌均有一定程度的抑菌效果,且对革兰阴性或阳性菌的抑菌效果没有明显差异。给感染卒倒杆菌的家蚕添食1.49 mg/mL和1.07 mg/mL生姜黄酮粗提液均具有一定的治疗作用,且效果略好于0.1 mg/mL蚕用盐酸诺氟沙星。此外,生姜黄酮粗提液用于蚕病防治对家蚕的生长发育无不良影响。     

Antibiotic growth promoters for the view of animal nutrition

From 01. 07./09. 1999 on six further antibiotic growth promoters have been banned--with only four substances remaining in this group of feed additives. Therefore, the discussion on a possible induction of bacterial resistance by antibiotic growth promoters, especially in potentially pathogenic bacteria, will sooner or later come to an end which is not least in the interest of the reputation of animal husbandry and food of animal origin. Unfortunately, no short-term solution for health problems by legislation--especially in the gastrointestinal tract--during rearing and the beginning of the fattening period is possible as experiences in Sweden have distinctively shown. Anyway, growth promoting feed additives were not a cure-all of rearing problems, in spite of their use considerable amounts of antibiotics were prescribed during this period. But growth promoters (especially chinoxalines) were most suitable for the prophylaxis of a microbial imbalance in the gastrointestinal tract. Therefore, after the ban of these effective representatives of feed additives the amount of prescribed antimicrobial drugs for metaphylaxis and therapy should be critically observed. The questions of practicable alternatives will be primarily addressed to the fields of animal nutrition, veterinary medicine and feed industry. To answer these questions and to evolve new solutions (as well as to check their suitability in practice) is considerably more intricate than simply to ban these substances which is more attractive for the media, however. It is no progressive solution to give up antimicrobial growth promoters as feed additives and to use the same substances (for example olaquindox) as therapeutics now (prescribed by veterinarians) or to switch to zincoxide or copper (in a dosage high above all nutrient requirements) in order to prevent postweaning problems due to E. coli. But one has to take into consideration the reasons for the use of antibiotics (growth promoters and therapeutics) or other "aids" (e.g. ZnO, Cu) in food producing animals (especially in beef-cattle, pigs and poultry) in "modern" production systems. The matter for conflict is the contrast between a minimised use of antimicrobial substances, as science as well as general public demand, and the requirements of "modern" livestock industry (rationalisation, increase in performance, specialisation, concentration) and general economy (save of resources, lowering of production costs). These well-known and expected problems arise in an almost exemplary manner in the case of antibiotic growth promoting feed additives. Therefore it is most difficult to impart suggestions to the persons involved as well as to the public.     

基于地黄研发水产动物免疫增强剂——地黄的免疫调节研究进展

传统的免疫增强剂,如左旋咪唑、催乳素等多属于化学合成或激素类物质。它们虽然通过增强养殖动物免疫力,提高了生产性能,但却降低了产品的营养价值,并可能危及食品安全,基于中草药研制的免疫增强剂应用于养殖业可解决这一难题。地黄对免疫系统具有广泛的药理作用:地黄多糖、低聚糖、水提液以及合剂等可通过调节免疫器官、免疫细胞和免疫分子的功能,平衡机体免疫系统。众多国内外学者开展了地黄的免疫调节研究,文中通过查阅大量国内外文献,综述了近年来地黄调节机体免疫作用的研究进展,以期为研制地黄类免疫增强剂提供参考。     

Synthetic immunostimulants (excluding sulfur-containing compounds)

Many different approaches have been used, over the last 15 years, for the design of potential immunostimulating drugs: Fractionation of crude natural substances (of eukaryotic or prokaryotic origin) already known to enhance immune functions, followed by chemical characterization and, in many cases, full synthesis of the active moiety: examples are provided by thymic hormones and the muramyldipeptide (MDP); Chemical modification of natural substances of known chemical structure in order to potentiate or change their biological activities or reduce their toxicity: murabutide, lipophilic MDP derivatives, lipopeptides (such as pimelautide), tuftsin analogs; Chemical synthesis (often without preconceived ideas about structure-activity relationship) of a great variety of molecules which are then screened in vitro and in vivo for immunopharmacological activity. The chemical structures and the biological profiles (in terms of possible primary cellular targets and mechanisms of immunostimulating activities) of representatives of class (b) and class (c) immunostimulants are reviewed in this paper.     

Characterization of outer membrane protein-enriched extracts from Pasteurella multocida isolated from turkeys

Outer membrane protein (OMP)-enriched extracts of avian strains of Pasteurella multocida were examined by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Culture medium did not have a significant effect on the OMP profiles of strains of P multocida examined; however, in vivo propagation had an appreciable effect on the OMP profile composition of the reference strain P-1059. Such bacteria, expressed several additional OMP in the 27-kD, 48-kD, 56-kD, 60-kD, 80-kD, and 94-kD molecular mass regions. These OMP were not detected in the electrophorogram of strain P-1059 grown in vitro. The OMP profiles of reference strains of the 16 serotypes of P multocida did not identify any serotype-specific protein markers. Field strains of serotype A:3 had variation in OMP profiles and did not express OMP that all were identical to that expressed by the reference strain P-1059. The live attenuated CU and M9 bacterial vaccine strains expressed strain-specific OMP markers of 48-kD and 45-kD molecular masses, respectively. These strain-specific OMP markers may be used to differentiate these strains from virulent field strains that are of the same serotype and isolated from turkeys that have succumbed to pasteurellosis as a result of vaccine-related reactions or breakdown in immunity.     

Mannheimia haemolytica and bovine respiratory disease

Mannheimia haemolytica is the principal bacterium isolated from respiratory disease in feedlot cattle and is a significant component of enzootic pneumonia in all neonatal calves. A commensal of the nasopharynx, M. haemolytica is an opportunist, gaining access to the lungs when host defenses are compromised by stress or infection with respiratory viruses or mycoplasma. Although several serotypes act as commensals, A1 and A6 are the most frequent isolates from pneumonic lungs. Potential virulence factors include adhesin, capsular polysaccharide, fimbriae, iron-regulated outer membrane proteins, leukotoxin (Lkt), lipopolysaccharide (LPS), lipoproteins, neuraminidase, sialoglycoprotease and transferrin-binding proteins. Of these, Lkt is pivotal in induction of pneumonia. Lkt-mediated infiltration and destruction of neutrophils and other leukocytes impairs bacterial clearance and contributes to development of fibrinous pneumonia. LPS may act synergistically with Lkt, enhancing its effects and contributing endotoxic activity. Antibiotics are employed extensively in the feedlot industry, both prophylactically and therapeutically, but their efficacy varies because of inconsistencies in diagnosis and treatment regimes and development of antibiotic resistance. Vaccines have been used for many decades, even though traditional bacterins failed to demonstrate protection and their use often enhanced disease in vaccinated animals. Modern vaccines use culture supernatants containing Lkt and other soluble antigens, or bacterial extracts, alone or combined with bacterins. These vaccines have 50-70% efficacy in prevention of M. haemolytica pneumonia. Effective control of M. haemolytica pneumonia is likely to require a combination of more definitive diagnosis, efficacious vaccines, therapeutic intervention and improved management practices.     

蒲公英提取物联合多种抗生素对奶牛乳房炎金黄色葡萄球菌的体外协同抑菌实验

为研究蒲公英提取物联合多种药物对奶牛乳房炎金黄色葡萄球菌的体外协同抑菌效果,以期应用于临床,减少抗菌药的使用量,降低细菌耐药性和兽药残留。试验选取3种来源(河北,东北,北京)的蒲公英提取物,通过高效液相色谱仪对3种不同来源的蒲公英提取物的主成分及含量进行测定并分析,选取后期试验所需的蒲公英提取物来源。并应用微量肉汤稀释法测定多种抗生素对金黄色葡萄球菌的MIC值(最小抑菌浓度),随后测试蒲公英提取物与抗菌药物联合用药,是否对金黄色葡萄球菌具有协同效果。试验结果表明,不同来源的蒲公英提取物主成分含量差异较大,含有单咖啡酰酒石酸、咖啡酸、菊苣酸、绿原酸,但含量比例不同。随之测得不同来源蒲公英提取物对金黄色葡萄球菌的敏感程度也有差异,临床用药前有必要进行药敏试验科学精准的选择更合适的药物。蒲公英提取物与金霉素、恩诺沙星、阿莫西林、氨苄西林、头孢噻呋、头孢喹肟等联合用药,对金葡菌的体外抑菌实验有良好的协同作用,体外能显著降低抗菌药物的用量。     

Human health aspects of antibiotic use in food animals: a review

Antibiotic use not only selects for resistance in pathogenic bacteria, but also in the commensal flora of exposed individuals. Veterinary surgeons regularly prescribe antibiotics for food animals to treat bacterial infections just as doctors do for human patients. In addition, however, animal feeds contain added antibiotics not for therapy but for economic reasons: to enhance the growth rate of these animals. Several of the antibiotics used as growth promoters are analogues of and fully cross resistant with important antibiotics used in human medicine. As a result of this high exposure to antibiotics, the prevalence of resistant bacteria in the faecal flora of these animals is high. These resistant bacteria can be directly and indirectly, via foods of animal origin, transferred to humans and either colonize the human intestinal tract or exchange their resistance genes with commensal bacteria of humans. As the intestinal flora functions as a reservoir of resistance genes for pathogenic bacteria and because many bacterial species of the intestinal flora are potential pathogens, the efficacy of antibiotic therapy in human medicine may be jeopardized.     

Single primer polymerase chain reaction fingerprinting for Pasteurella multocida isolates from laboratory rabbits

OBJECTIVE: To evaluate a rapid polymerase chain reaction (PCR) fingerprinting technique for discriminating among Pasteurella multocida isolates from laboratory rabbits. SAMPLE POPULATION: 33 P multocida isolates from rabbits with clinical pasteurellosis. PROCEDURE: PCR assays were conducted with 2 minisatellites (core sequence and modified core sequence of phage M13) and 2 microsatellites ([GTG]5 and [GACA]4). Each bacterium was assigned to a PCR type for each of the primers used. Boiled bacterial extracts and purified genomic DNA were compared by use of PCR assays for phage M13 and (GACA)4. Plasmids were isolated from each bacterium, and their influence on PCR fingerprint was determined, using boiled extracts as a DNA source. RESULTS: M13 core sequence and M13 modified core sequence yielded 5 and 8 PCR types, respectively. The microsatellites (GTG)5 and (GACA)4 yielded 4 and 9 PCR fingerprint types, respectively. Fingerprint patterns obtained by use of isolated DNA differed from those obtained by use of boiled extracts, although discrimination among P multocida isolates was similar. The presence or absence of plasmids did not affect PCR fingerprints. CONCLUSION: Single primer PCR fingerprinting with minisatellite and microsatellite primers is an efficient and reproducible method for the discrimination of P multocida isolates from rabbits and can be performed directly, using boiled bacterial extracts as a source of template, although more bands were obtained from pure genomic DNA.     

Chemistry of immunomodulators

A large number of synthetic derivatives, inorganic compounds or naturally occurring substances are able to depress, regulate or enhance the immune response. Immunomodulators, among which some are chemically well defined and others are complex preparations, exhibit a great variety of chemical structures which are briefly reviewed, without details on their immunopharmacological properties. These molecules allow access to a new type of therapy which aims at acting on the host defense mechanisms.     

An improved Corynebacterium pseudotuberculosis vaccine for sheep

Extensive experiments in mice confirmed that the immunogenicity of a Corynebacterium pseudotuberculosis vaccine could not be significantly improved with the use of various adjuvants. Immunity against C. pseudotuberculosis likewise could not be enhanced by incorporating various immunostimulants into the vaccine or by the use of live vaccines. However, a combination of aluminium hydroxide gel and saponin as adjuvant did have a beneficial effect. This vaccine was tolerated better, and a smaller dose apparently protected sheep more effectively against intralymph node challenge than the currently available alum-precipitated vaccine.