In vitro effect of levamisole on the cell viability,phagocytosis and respiratory burst of Barbel chub (Squaliobarbus curriculus) macrophages

The present study was to determine in vitro effect of levamisole on the immune functions of Barbel chub (Squaliobarbus curriculus), head–kidney‐derived (HKM), spleen‐derived (SM) and peripheral blood monocyte‐derived macrophage (PBM). Macrophages were incubated with levamisole 10³, 10¹, 10⁻¹ and 10⁻³ ng mL⁻¹ to assay the cell viability, respiratory burst and phagocytosis. The results showed that macrophages treated with levamisole 10⁻³ ng mL⁻¹ gave a maximum respiratory burst response, whereas levamisole 10³ ng mL⁻¹ had no effect. Phagocytosis activity of the macrophages treated with levamisole enhanced significantly when compared to control, maximum response being at 10⁻³ ng mL⁻¹. While using the methylthiazoletetrazolium method to measure the cell activity for 12, 24, 36, 48, 60 h, there was no significant role on proliferation and the cell viability began to decline after 24 h. In conclusion, levamisole is a potent enhancer of Barbel chub macrophage activity with low concentration.     

复方左旋咪唑浇注剂在山羊体内的药代动力学研究

研究了山羊涂皮给予复方左旋咪唑浇注剂(0 1mL/kg)后,血浆中左旋咪唑的药物动力学特征。本项研究采用高效液相色谱法,色谱条件是以μBond-C18(2×250mm)为固定相,甲醇:0 05mol/L碳酸铵(65∶35,v/v)为流动相,225nm为检测波长。左旋咪唑血药浓度经药代动力学分析表明,其血药浓度的经-时过程符合一级吸收一室开放模型,动力学方程为:C =3 894(e-0 157t-e-0 340t),达峰时间(Tmax)为4 326h,峰浓度(Cmax)为0 916μg/mL,曲线下面积(AUC)为11 015μg/(mL·h)。     

Dietary levamisole modulates the immune response and disease resistance of Asian catfish Clarias batrachus (Linnaeus)

In order to determine the immunomodulatory effect of dietary levamisole in Asian catfish (Clarias batrachus), fish were fed four different diets for 10 days: a formulated diet as control and the same diet supplemented with 50, 150 or 450 mg levamisole kg^?1 feed. The serum bacterial agglutination titre against Aeromonas hydrophila as a measure of specific immunity, serum haemagglutination titre, natural haemolytic complement activity (ACH₅₀), myeloperoxidase and lysozyme activities, total protein level and oxidative radical production by neutrophils as a measure of non‐specific immunity as well as disease resistance against A. hydrophila challenge to separate vaccinated and non‐vaccinated groups were evaluated at 0, 1, 2 and 3 weeks after last administration of levamisole. Levamisole supplement at the lowest level (50 mg kg^?1) significantly enhanced oxidative radical production and serum myeloperoxidase (MPO) content immediately after 10 days of feeding, which reached peak values after 3 and 2 weeks of feeding respectively. Haemolytic complement and haemagglutination titre were significantly enhanced after 3 and 1 weeks respectively. Haemolytic complement activity and MPO activities were significantly raised to 150 mg kg^?1 after 3 and 2 weeks, respectively. At the highest level of levamisole feeding (450 mg kg^?1) significant decreases in superoxide production and complement activity were measured immediately after levamisole feeding, which returned to the normal level after 1 week post‐ feeding. Fish were challenged with a virulent strain of A. hydrophila at 0, 1, 2 and 3 weeks after levamisole feeding, and the cumulative per cent survival was recorded over 10 days. Feeding levamisole at 50, 150 or 450 mg kg^?1 increased per cent survival in vaccinated fish immediately after levamisole feeding, and survival was significantly higher at 450 mg kg^?1. There was no difference in mortality patterns in non‐vaccinated fish. The results support the use of levamisole at 50 mg kg^?1 feed for 10 days as an immunostimulant in Asian catfish farming.     

林可霉素注射液非法添加盐酸左旋咪唑的HPLC检测方法研究

建立了兽用林可霉素注射液中非法添加盐酸左旋咪唑的高效液相色谱检测方法。采用Waters Atlantis? T3 C18(4.6×250mm, 5μm)色谱柱分离,以磷酸二氢钠溶液-甲醇(70:30)作为流动相进行等度洗脱（流速1.00mL/min）,用二极管阵列检测器在230nm波长处进行测定。考察了此色谱条件下方法的专属性、线性、回收率、精密度、检测限和耐用性。结果表明,盐酸左旋咪唑在进样浓度为0.02mg/mL～0.4mg/mL时呈良好的线性关系,R2=0.9999;重复性试验RSD为0.6%;平均回收率为99.7%;检测限为 0.0002mg/mL,定量限为0.0016mg/mL。该法准确、简便、可行,适用于林可霉素注射液中盐酸左旋咪唑的检测。     

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep

Objective: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics.
Design: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials.
Procedure: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50 000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack.
Results: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction tests overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm.
Conclusion: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.     

Pharmacokinetics of levamisole in the red‐eared slider turtles (Trachemys scripta elegans)

The pharmacokinetics and bioavailability of levamisole were determined in red‐eared slider turtles after single intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. Nine turtles received levamisole (10 mg/kg) by each route in a three‐way crossover design with a washout period of 30 days. Blood samples were collected at time 0 (pretreatment), and at 0.25, 0.5, 1, 1.5, 3, 6, 9, 12, 18, 24, 36, and 48 hr after drug administration. Plasma levamisole concentrations were determined by a high‐performance liquid chromatography assay. Data were analyzed by noncompartmental methods. The mean elimination half‐life was 5.00, 7.88, and 9.43 hr for IV, IM, and SC routes, respectively. The total clearance and volume of distribution at steady state for the IV route were 0.14 L hr^?1 kg^?1 and 0.81 L/kg, respectively. For the IM and SC routes, the peak plasma concentration was 9.63 and 10.51 μg/ml, respectively, with 0.5 hr of T_max. The bioavailability was 93.03 and 115.25% for the IM and SC routes, respectively. The IM and SC route of levamisole, which showed the high bioavailability and long t_1/2?z, can be recommended as an effective way for treating nematodes in turtles.     

Suspected levamisole intoxication in calves

CASE HISTORY: A group of 32 Friesian and four Hereford calves, 3–4 months old with body weights between 100–120?kg, were purchased from a weaner sale. On arrival at the property the Hereford calves were treated with a combination anthelmintic containing 2?g/L abamectin and 80?g/L levamisole hydrochloride. Shortly afterwards they developed tremors and frothing from the mouth, and two died overnight. The Friesian calves were treated with the same anthelmintic on the following day, when some showed hypersalivation and frothing from the mouth.

CLINICAL FINDINGS: Examination of the three most severely affected Friesian calves revealed severe nicotinic-type symptoms including hypersalivation, frothing from the mouth, muscle tremors, recumbency, rapid respiration, hyperaesthesia, and central nervous system depression. Other calves showed mild to moderate signs of intoxication including restlessness, tail switching, salivation, tremors, frequent defaecation, mild colic and jaw chomping. Two calves died shortly afterwards. An adverse drug event investigation revealed that the formulation and quality of the anthelmintic was within the correct specification, and that the drench gun was functioning correctly.

DIAGNOSIS: Suspected levamisole intoxication due to a combination of possible overdosing, dehydration, and stress caused by transportation and prolonged yarding.

CLINICAL RELEVANCE: Susceptibility to levamisole toxicity in New Zealand calves can be increased if factors like dehydration or stress are present. Levamisole has a narrow margin of safety, and overdosing in calves can easily occur if the dose rate is not based on their actual weight or health status.     

Les immunostimulants orientent la reponse locale au virus de l''I.B.R. vers la production d''Interferon

Immuno-adjuvants like MDP or levamisole inoculated in the calf through general route increase the respiratory mucosa response to the irradiation inactivated IBRV.

We have shown from the 2nd day of the inoculation an interferon activity in the nasal mucus. This interferon partially destroyed at pH2 and at 56°C, persists in the respiratory fluids for one week. It is never found in the sera of the animals.

This inactivated virus given through nasal route does not stimulate antibody production in the local system or in the serum.

The dose of levamisole administered is critical: 5 mg/kg are the minimal quantity required to give a favourable answer whereas the 2.5 mg/kg normally used are without effect.

The interferon presence in the respiratory fluids gives a satisfactory interpretation of the good resistance to respiratory infection obtained in 500 calves with this treatment: inactivated virus by nasal route and immuno-adjuvant by intradermic or intramuscular route.     

动物左旋咪唑中毒与解救

左旋咪唑是效果很好的驱除动物寄生虫的药物,但使用不当极易造成中毒。本文介绍了不同动物发生左旋咪唑中毒后的临床症状以及解救方法,旨在为临床应用提供参考。     

Masking the taste of the conditioned taste aversion agent levamisole using an ion-exchange resin, for practical application in wildlife management

For a conditioned taste aversion (CTA) agent to be successful in wildlife management applications, the compound must not be detectable by the animal. Levamisole is an effective CTA agent when administered by oral intubation, but it is readily detected by a number of species when mixed directly in food. This paper describes the development of an ion-exchange resin complex (resinate) to mask the taste of levamisole. Two different resins were evaluated, Amberlite IRP-64 and Amberlite IRP-69, and release studies indicated that the resinate formed using IRP-64 resin would be most suitable for use in wildlife management. Although it contained a relatively low loading of levamisole (77 g kg(-1)), the results indicated that the IRP-64 resinate should be stable in the mouth and release the levamisole quickly in the acid environment of the stomach (93% of levamisole was released into 0.1 M HCl in 5 min). In a bioassay using laboratory rats (Rattus norvegicus Berk), we showed that the taste of levamisole was successfully masked in a biscuit bait using the IRP-64 resinate and that a CTA was generated to untreated bait. The use of ion-exchange resins is a new approach in the taste-masking of CTA agents and could be applied to other wildlife management applications.