Serum,milk, and tissue monensin concentrations in cattle with adequate and potentially toxic dietary levels of monensin: pharmacokinetics and diagnostic interpretation

Used in both beef cattle and dairy cows, monensin can provide many health benefits but can, when unintended overexposures occur, result in adverse effects. Information on serum and tissue concentrations following overexposure and/or overt toxicosis which may aid in diagnostics and clinical outcome is lacking. The aim of this study was to determine concentrations of monensin in biological specimens following oral exposure for 10 days to an approved dose (1 mg/kg) and a higher dose (5 mg/kg) of monensin given daily on a body weight basis to 10 dairy cows. No deaths were reported; cows receiving 5 mg/kg showed early signs of toxicosis including depression, decreased feed intake, and diarrhea after 4 days of exposure. Histopathological findings were minimal in most cows. Pharmacokinetic modeling of the detected serum concentrations for the 1 and 5 mg/kg dose groups determined the C_max, T_max, and t_1/2λ to be 0.87 and 1.68 ng/mL, 2.0 and 1.0 h, and 1.76 and 2.32 days, respectively. Mixed regression models showed that the dose level and days since last dose were significantly associated with monensin concentrations in all four tissues, and with cardiac troponin levels. The high dose resulted in a significant elevation of monensin in tissues at approximately 4.7 times compared to the monensin concentrations in the tissues of animals from the low‐dose group. The cTnI concentrations in the high‐dose group were 2.1 times that of cTnI in the low‐dose group. Thus, the ability to diagnose monensin overexposure and/or toxicosis will improve from knowledge of biological monensin concentrations from this study.     

Specific polyphenol oxidase activity of red clover (Trifolium pratense) and its relation with forage quality in field experiments

Abstract

In feeding studies, red clover (RC) influenced positively the N utilization by ruminants. A relationship between polyphenol oxidase (PPO) activity and forage quality has not been established. Our objective was to investigate seasonal, site, genotype, and management effects on specific PPO activity in RC in three experiments under field conditions, and relate the activity to forage-quality parameters. In Experiment 1, six RC genotypes at two study sites were submitted to a 3-cut system. Specific PPO activity, forage quality, and vegetation stage were determined. PPO activity varied between harvest and study sites, with genotypes differing up to 3-fold in PPO activity within harvests. The specific PPO activity, forage quality, and vegetation stage in RC subjected to 5-cut system and grazing (Experiment 2) were determined. Additionally, in Experiment 3, cutting frequency in RC swards including mechanical stress (rolling) was investigated. The induction of PPO activity in RC by grazing or mechanical stress (Experiments 2 and 3) increased the activity up to 2.5-fold compared with RC at similar vegetation stage submitted to the 5-cut system. Mechanical stress induced by grazing or rolling, and seasonal differences, seem to have a larger influence on specific PPO activity than does the genotype effect observed in Experiment 1. For forage quality, an increased specific PPO activity explained 29–46% of the reduction in protein fraction ‘A’ content (non-protein N) in the cutting systems in Experiments 2 and 3. Other CP fractions achieved a lower relation. Furthermore, the precipitation-to-temperature ratio preceeding a harvest explained 63% of the variation in the specific PPO activity. In conclusion, the PPO activity in RC is induced by grazing and rolling. Whereas weather conditions preceeding a harvest showed a large influence, genotype influence had only minor relevance. These results may have implications for regional harvest management towards efficient N utilization by ruminants.     

Diagnosis of Taxus (yew) poisoning in a horse.

A 2-year-old bay Thoroughbred colt was found dead overnight in its stall without a known history of any illness, existing disease, or toxicant exposure. No information on the clinical signs before this animal's death was reported. A full necropsy was performed the next morning and revealed a mild to moderate degree of endocardial hemorrhages in both ventricles. Microscopic examination of the heart showed an acute mild multifocal necrosis of papillary muscles and ventricles. The stomach content contained approximately 2% Taxus alkaloids as determined by gas chromatography/mass spectrometry. In the past, diagnosis of Taxus poisoning has been mainly based on history of exposure and the presence of plant parts in the gastrointestinal tract. Pathological lesions associated with Taxus poisoning have not been published for horses. Therefore, this is the first report of cardiac lesions in a horse after lethal exposure to Taxus. On the basis of these findings, it is suggested that Taxus exposure needs to be considered in the differential diagnosis of horses that die suddenly or have cardiac lesions suggestive of Taxus exposure, even if intact plant parts are not identified in the stomach by the naked eye.     

Über einige Fälle von Anophthalmie bei Kälbern des Deutschen Braunviehs

This is a report on five cases of anophthalmia (in one case accompanied by hydrocephalus and anomalies of the cerebrum) in Brown Swiss cakes. The anomalies occured within four months in two herds. Clinical signs, anatomical and histological findings are described. It was not possible to determine the cause as a hereditary condition or as an exogenous teratogenic factor.     

Efficacy of milbemycin oxime in the treatment of canine generalized demodicosis: a retrospective study of 99 dogs (1995-2000)

Ninety-nine dogs diagnosed with generalized demodicosis were treated with milbemycin oxime. Cases diagnosed before two years of age were classified as juvenile-onset (53%) and those diagnosed after two years of age as adult-onset (47%). Dogs were considered cleared of mites when none could be demonstrated in scrapings and cured if no relapse was seen for 12 months. Eighty-five per cent (84/99) were cured with milbemycin oxime used for 1-6 months (mean 2.3 months) at a dosage of 0.5-1.6 mg kg-1 body weight (mean 0.75 mg kg-1). No significant difference in dosage or treatment time was seen between juvenile and adult cases. Chance of cure was significantly better in young animals (cured cases mean age 2.97 years) than in older animals (not cured cases mean age 8.02 years). Start of treatment early in the course of disease gave a significantly better chance of cure. Cases with severe pododemodicosis had less chance of a cure (9/11 not cured).     

Myopathy in brown pelicans (Pelicanus occidentalis) associated with rancid feed

Three adult brown pelicans (Pelicanus occidentalis) were observed to be weak, anorexic and unresponsive to antibiotics, anti-inflammatory drugs, vitamins including vitamin E, and steroids. Blood chemistry revealed high activities of aspartate aminotransferase, creatinine kinase and lactate dehydrogenase. Radiographs of the birds' leg muscles revealed multiple opacities suggestive of calcification; the gross lesions included white streaks in the leg, wing, and heart muscles, and the microscopical lesions consisted of various degrees of degeneration and necrosis characterised by eosinophilia, variations in fibre size, loss of striations, myolysis, mineralisation, and proliferation of mononuclear cells in the skeletal muscles and the myocardium. The levels of heavy metals, selenium and vitamin E in the birds' livers were not abnormal. The level of peroxide in their diet of capelin fish was high, 69 meq/kg, (normal <20 meq/kg) consistent with rancid feed, and the level of vitamin E was very low, 0.5 iu/kg (normal 20 to 30 iu/kg). It was concluded that the myopathy was probably caused by vitamin E deficiency due to feeding the pelicans a rancid diet.     

Vitamin A deficiency in turkey poults.

Vitamin A deficiency was diagnosed in a commercial flock of 13,000 4-6-week-old turkey poults in the summer of 2004. The birds were initially submitted for examination because of a 3% increase in the reported daily mortality of the flock. Clinically, affected birds had stunted growth and ruffled feathers, showed signs of incoordination, and were depressed. At necropsy, pale white pseudomembranous to mucoid material was observed on the mucosal surface of the tongue, oral cavity, portions of the esophagus, and the crop of some birds. Histologically, there was squamous metaplasia of the mucosal epithelium of the oral mucosa, esophagus, sinuses, nasal glands, bronchi, proventriculus, and the bursa of Fabricius. Vitamin A was not detected in the feed sample at a detection limit of 0.5 mg/kg. Serum vitamin A concentrations in 7 birds were very low and ranged from 0.05 to 0.1 mg/L. Vitamin A concentrations in livers were extremely low (0.1 mg/kg wet weight, 1/7 poults) or undetectable (< 0.1 mg/kg wet weight, 6/7 poults). A diagnosis of vitamin A deficiency was made based on gross and microscopic lesions and vitamin A concentrations in serum, liver, and feed. To the authors' knowledge, this is the first documented case of vitamin A deficiency in poults submitted from a commercial meat turkey producer comparatively depicting the gross and microscopic lesions with those found in other species of birds and mammals.     

Assessment of melamine and cyanuric acid toxicity in cats.

The major pet food recall associated with acute renal failure in dogs and cats focused initially on melamine as the suspect toxicant. In the course of the investigation, cyanuric acid was identified in addition to melamine in the offending food. The purpose of this study was to characterize the toxicity potential of melamine, cyanuric acid, and a combination of melamine and cyanuric acid in cats. In this pilot study, melamine was added to the diet of 2 cats at 0.5% and 1%, respectively. Cyanuric acid was added to the diet of 1 cat at increasing doses of 0.2%, 0.5%, and 1% over the course of 10 days. Melamine and cyanuric acid were administered together at 0%, 0.2%, 0.5%, and 1% to 1 cat per dose group. No effect on renal function was observed in cats fed with melamine or cyanuric acid alone. Cats dosed with a combination were euthanized at 48 hours after dosing because of acute renal failure. Urine and touch impressions of kidneys from all cats dosed with the combination revealed the presence of fan-shaped, birefringent crystals. Histopathologic findings were limited to the kidneys and included crystals primarily within tubules of the distal nephron, severe renal interstitial edema, and hemorrhage at the corticomedullary junction. The kidneys contained estimated melamine concentrations of 496 to 734 mg/kg wet weight and estimated cyanuric acid concentrations of 487 to 690 mg/kg wet weight. The results demonstrate that the combination of melamine and cyanuric acid is responsible for acute renal failure in cats.     

Changes in compact bone microstructure of rats subchronically exposed to cadmium

Background

Chronic exposure to cadmium (Cd), even at low concentrations, has an adverse impact on the skeletal system. Histologically, primary and secondary osteons as basic structural elements of compact bone can also be affected by several toxicants leading to changes in bone vascularization and mechanical properties of the bone. The current study was designed to investigate the effect of subchronic peroral exposure to Cd on femoral bone structure including histomorphometry of the osteons in adult male rats.In our study, 20 one-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males received a drinking water containing 30 mg of CdCl₂/L, for 90 days. Ten one-month-old males without Cd intoxication served as a control group. After 90 days of daily peroral exposure, body weight, femoral weight, femoral length, cortical bone thickness and histological structure of the femora were analysed.

Results

We found that subchronic peroral application of Cd had no significant effect on body weight, femoral length and cortical bone thickness in adult rats. On the other hand, femoral weight was significantly increased (P < 0.05) in Cd-intoxicated rats. These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta and supplied primary and secondary osteons. Additionally, a few resorption lacunae which are connected with an early stage of osteoporosis were identified in these individuals. Histomorphometrical evaluations showed that all variables (area, perimeter, maximum and minimum diameter) of the primary osteons’ vascular canals, Haversian canals and secondary osteons were significantly decreased (P < 0.05) in the Cd group rats. This fact points to alterations in bone vascularization.

Conclusions

Subchronic peroral exposure to Cd significantly influences femoral weight and histological structure of compact bone in adult male rats. It induces an early stage of osteoporosis and causes reduced bone vascularization. Histomorphometrical changes of primary and secondary osteons allow for the conclusion that the bone mechanical properties could be weakened in the Cd group rats. The current study significantly expands the knowledge on damaging action of Cd on the bone.