Synergism of macrocyclic lactones against Haemonchus contortus.

A possible synergistic effect of macrocyclic lactones' (MLs) combination has been previously described against resistant gastrointestinal nematodes of cattle. In addition to synergism, drug-drug interactions between MLs can also result in additive or antagonistic effect, considering the different MLs pharmacokinetics, pharmacodynamics, and interactions with molecular mechanisms of resistance. Therefore, the aim of the current work was evaluated the effect of different MLs combinations against Haemonchus contortus. Infecting larvae of two isolates (one susceptible and one resistant to ivermectin) were used in the larval migration inhibition test. After estimating the half maximal effective concentration of abamectin (ABA), eprinomectin, (EPR), ivermectin (IVM), and moxidectin (MOX) for both isolates, combinations were delineated by a simplex-centroid mixture experiment, and the mixture regression analysis was applied to the special cubic model. A synergistic effect was found for the EPR + MOX against the susceptible isolate as well as the EPR + MOX, IVM + MOX, and ABA + EPR + IVM against the resistant isolate. An antagonistic effect of ABA + IVM + MOX was found against the susceptible isolate. For the susceptible isolate, a higher inhibition was found with greater proportions of EPR and lower proportions of the other drugs compared to the reference mixture. For the resistant isolate, inhibition greater than that of the reference mixture was found with higher proportions of IVM as well as lower proportions of the other drugs. The synergistic and antagonistic effects were dependent on the following: (a) parasite drug resistance profile, (b) the composition of the combination, and (c) the proportions used, with EPR and IVM exerting a greater impact on these effects.

Aerobic dissipation of avermectins and moxidectin in subtropical soils and dissipation of abamectin in a field study.

Avermectins and moxidectin are antiparasitics widely used as active pharmaceutical ingredients in veterinary medicine, as well as in pesticide formulations for pest control in agriculture. Although the use of these compounds provides benefits to agribusiness, they can impact the environment, since a large part of these substances may reach the soil and water from the excreta of treated animals and following direct applications to crops. The present work had the objective of evaluating the dissipation behaviors of abamectin, doramectin, eprinomectin, ivermectin, and moxidectin in four native Brazilian soils of different textural classes (clay, sandy-clay, sandy, and sandy-clay-loam), following OECD Guideline 307. The studies were conducted in a climate chamber at 22 °C, 71% relative humidity, and protected from light. The dissipation studies were carried out with all drugs together, since no difference was verified when studies were done with each drug separately. The concentrations of the drugs in the soils were determined using an ultra-high performance liquid chromatograph coupled to a fluorescence detector or a tandem mass spectrometer. The dissipation half-life (DT50) values ranged from 9 to 16 days and the calculated GUS index values were in the range from -1.10 to 0.08, indicating low mobility of the drugs in the soils evaluated and low tendency for leaching. In addition, a field study was carried out to evaluate the dissipation of abamectin after application of a foliar pesticide in an orange crop. A DT50 of 9 days was determined, which was similar to that obtained under controlled conditions in the climate chamber (12 days), indicating that biotransformation was the primary process influencing the overall dissipation.

Development and validation of a method for simultaneous determination of trace levels of five macrocyclic lactones in cheese by HPLC-fluorescence after solid-liquid extraction with low temperature partitioning.

A highly sensitive analytical method was developed and validated, following international guidelines, for the determination of the residues of five macrocyclic lactones (MLs) (abamectin, doramectin, eprinomectin, ivermectin and moxidectin) in cheese. The extracts were concentrated by rotary-evaporation and derivatized; no clean-up was necessary. Despite matrix complexity, no significant matrix-effect was verified, and standards were prepared in solvents. Linear working ranges varied from 0.25 to 5.0 µg L-1. Excellent limits of quantification (0.58-0.87 µg kg-1), mean recoveries (91-103%), and repeatability and intermediate precision (<5.8%) were obtained. Twenty-two samples of bovine and non-bovine cheeses were analyzed. Twenty-one samples showed residues of at least one ML (between 0.59 and 15.3 µg kg-1), but moxidectin was never detected; a sample of mozzarella was free of MLs. To the best of our knowledge, this is the first method describing the simultaneous evaluation of these MLs in cheese using HPLC and fluorescence detection.

On-line solid-phase extraction-ultra high performance liquid chromatography-tandem mass spectrometry for the determination of avermectins and milbemycin in soils.

Avermectins and milbemycin are widely used as veterinary drugs and as agricultural pesticides, and their residues have been detected in soil. This study reports a simple and high-throughput method for determining ivermectin (IVER), abamectin (ABA), doramectin (DORA), eprinomectin (EPRI), and moxidectin (MOXI) residues in soils, employing an on-line solid-phase extraction technique coupled with ultra-high performance liquid chromatography and tandem mass spectrometry (SPE-UHPLC-MS/MS). The method was validated and applied for the determination of ABA in soils from an orange plantation treated with this pesticide. The sample preparation procedure consisted of extraction of the compounds from soil using methanol (with recoveries of 73-85%), and subsequent on-line SPE cleanup and concentration using a C8 sorbent coupled to the UHPLC-MS/MS system. The optimal conditions were: water:methanol (40:60, v/v) sample solvent; water:methanol (96:4, v/v) loading solvent; 2×250µL sample volume; and elution of the analytes retained on the SPE column in back flush with 5mmolL-1 ammonium acetate:acetonitrile (10:90, v/v) chromatographic mobile phase. The method produced linear results in the ranges 0.1-10ngg-1 (IVER, ABA, DORA, and MOXI) and 0.5-10ngg-1 (EPRI), with linearity greater than 0.99. The precision of the method was better than 19% and accuracy was in the range 74-89%. The limits of quantitation were 0.2ngg-1 for EPRI and 0.1ngg-1 for the other compounds. The SPE column could be reused in more than 2000 analyses without loss of efficiency. The ABA concentration in the soil varied between 1.7 and 18ngg-1, and no dissipation was observed during five consecutive days after application of the pesticide to the orange plantation.

Dysphagia secondary to Spirocerca lupi in a German shepherd dog

Background: Spirocerca lupi is a nematode that causes nodules in the esophagus and aortic aneurysms in dogs. Animals are infected by eating intermediate host (beetle) containing infective larvae or consuming viscera containing parasitic cysts from paratenic hosts. Dogs commonly have a subclinical presentation, but the most common signs are vomiting and regurgitation. Visualizing nodules or neoplastic masses via esophagoscopy and the presence of S. lupi eggs in feces are the best diagnostic methods. Milbemycin oxime is effective as a treatment for S. lupi. The objective of this study was to describe the diagnostic and medical management of a patient with dysphagia secondary to esophageal S. lupi nodules.Case: A 7-year-old male German shepherd dog was referred for endoscopic examination. The animal presented with chronic severe dysphagia and weight loss with a presumptive diagnosis of an esophageal foreign body. At palpation of the neck, the dog was painful just dorsal to the cricoid cartilage and had submandibular lymphadenomegaly. The animal also exhibited a dropped jaw which could be returned to its normal position by manipulation. Radiographic examination demonstrated a radiopaque image compatible with a mass in the cranial esophagus just caudal to the upper esophageal sphincter. A fluoroscopy study was performed and confirmed the presence of a mass apparently within the [...](AU)

Dysphagia secondary to Spirocerca lupi in a German shepherd dog

Background: Spirocerca lupi is a nematode that causes nodules in the esophagus and aortic aneurysms in dogs. Animals are infected by eating intermediate host (beetle) containing infective larvae or consuming viscera containing parasitic cysts from paratenic hosts. Dogs commonly have a subclinical presentation, but the most common signs are vomiting and regurgitation. Visualizing nodules or neoplastic masses via esophagoscopy and the presence of S. lupi eggs in feces are the best diagnostic methods. Milbemycin oxime is effective as a treatment for S. lupi. The objective of this study was to describe the diagnostic and medical management of a patient with dysphagia secondary to esophageal S. lupi nodules.Case: A 7-year-old male German shepherd dog was referred for endoscopic examination. The animal presented with chronic severe dysphagia and weight loss with a presumptive diagnosis of an esophageal foreign body. At palpation of the neck, the dog was painful just dorsal to the cricoid cartilage and had submandibular lymphadenomegaly. The animal also exhibited a dropped jaw which could be returned to its normal position by manipulation. Radiographic examination demonstrated a radiopaque image compatible with a mass in the cranial esophagus just caudal to the upper esophageal sphincter. A fluoroscopy study was performed and confirmed the presence of a mass apparently within the [...]